Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
Open accessAbstract
Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some contacts between PcG-associated regions, including poised promoters and enhancers in ESCs, are retained after these regions are activated during cell differentiation.
“Notably, some contacts between PcG-associated regions, including poised promoters and enhancers in ESCs, are retained after these regions are activated during cell differentiation [141, 143].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
The Results section on rewiring and recolouring (Figure 6E–F; page not available) reports that some promoter interactions persist during ESC-to-NEC differentiation, including an IRX3 interaction whose promoter-interacting region changes from repressed to active. The Results section on regulatory elements also reports contacts between poised or Polycomb-associated promoters and similarly marked regions. The copy does not establish that the retained contacts specifically join poised promoters and enhancers that both become activated. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe chromatin state of the promoter at dual-state CRUs typically corresponded to the majority state of its enhancers, consistent with competition of opposing regulatory effects at the promoters.
“the chromatin state of the promoter at dual-state CRUs typically corresponded to the majority state of its enhancers, consistent with a competition of opposing regulatory effects at the promoters.”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
The Results section on CRU reorganisation reports that a promoter’s chromatin state generally matched the most prevalent state among its interacting regions. The Discussion section on regulation by multiple enhancers interprets this as possible ‘majority vote’ signal integration, but does not establish competition between opposing regulatory effects; it also offers independent enhancer action and promoter-state turnover as possible explanations. Page numbers are unavailable in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredUpon early neural differentiation, about a third of single-state CRUs in human ESCs became dual-state, while around half of all dual-state CRUs became single-state.
“Upon early neural differentiation, about a third of single-state CRUs in human ESCs became dual-state, while around half of all dual-state CRUs became single-state [141].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
The Results section (‘ESC differentiation is associated with the dynamic reorganisation of CRUs’; page unavailable) confirms that CRUs gained and lost dual-state configurations during ESC-to-NEC differentiation. But its figures use different denominators: 65% of initially single-state CRUs remained single-state, while 13% and 11% of CRUs acquired and lost dual-state configurations, respectively. It does not establish that a third of initially single-state CRUs became dual-state or that half of initially dual-state CRUs became single-state. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome enhancers are marked with H3K27me3 alone and are considered to be Polycomb-repressed.
“Finally, some enhancers are marked with H3K27me3 alone and are considered to be “Polycomb-repressed” [139–141].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
In mammals, PcG-associated promoters and enhancers engage in multitudes of looping contacts, particularly in early development.
“In mammals, PcG-associated promoters and enhancers also engage in multitudes of looping contacts, particularly in early development [139, 141, 276, 357].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
In mammalian differentiation models, extensive remodelling of enhancer-promoter contacts is typically observed consistently with enhancer activation.
“In mammalian differentiation models, in contrast, extensive remodelling of enhancer–promoter contacts is typically observed consistently with enhancer activation [141, 394–397].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
A significant minority of enhancers in human ESCs show pre-existing "permissive" promoter contacts prior to activation.
“Nonetheless, a significant minority of enhancers in human ESCs also show pre-existing “permissive” promoter contacts prior to activation [141, 394].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
Capture Hi-C analyses in multiple cell types consistently detect enhancer-promoter contacts that cross TAD boundaries.
“Capture Hi-C analyses in multiple cell types consistently detect enhancer–promoter contacts that cross TAD boundaries [141, 243].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
20% of CRUs detected in human ESCs and early ES-derived neural progenitors were dual-state, containing a mixture of active and poised or Polycomb-repressed enhancers.
“with 20% of CRUs detected in these cells being “dual-state”, i.e. containing a mixture of active and poised or Polycomb-repressed enhancers [141].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
Changes in CRU state were predominantly driven by coordinated alterations in chromatin state of enhancers and their promoter contacts, and were associated with significant changes in gene expression.
“Changes in CRU state were predominantly driven by coordinated alterations in the chromatin state of enhancers and their promoter contacts, and were associated with significant changes in gene expression [141].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
Enhancers vastly outnumber promoters in human and mouse genomes, and promoters often contact more than one enhancer in the same cell type.
“Enhancers vastly outnumber promoters in human and mouse genomes [131], and consistently promoters often contact more than one enhancer in the same cell type [141, 243, 278, 279].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
Analyses in human ESCs and early ES-derived neural progenitors found that enhancers within a CRU tended to have the same activity state in a given cell type.
“Analyses in human ESCs and early ES-derived neural progenitors found that, as expected, enhancers within a CRU tended to have the same activity state in a given cell type [141].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [141]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 4× · see citing works
“Genes differentially expressed between ESCs and NECs were identified using DESeq2 (FDR < 0.05 and a log2 fold change of >1.5).”
InfluentialAn integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · cited 1× · see citing works
“7 (http://homer.salk.edu/homer/) (Heinz et al., 2010).”
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400 · cited 1× · see citing works
“Data were converted to GRCh37 using liftOver (Kent et al., 2002).”
MethodComprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898 · cited 1× · see citing works
“A/B compartments were called by computing the principal components of the distance- and coverage-corrected interaction profile correlation matrix at 250 kb resolution (Lieberman-Aiden et al., 2009).”
MethodTopological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · cited 2× · see citing works
“TADs were identified based on directionality indices (Dixon et al., 2012) of Hi-C interactions 1 Mb upstream and downstream from a 25 kb sliding window every 5 kb steps, which were then smoothed using a running average over a ± 25 kb window.”
MethodIntegrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · cited 1× · see citing works
“The definition of chromatin signatures has enabled the genome-wide identification of enhancer elements across multiple human cell types (ENCODE Project Consortium, 2012; Heintzman et al., 2007, 2009; Pennacchio et al., 2006; Rada-Iglesias et al., 2011; Kundaje et al., 2015).”
BackgroundHistone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302 · cited 1× · see citing works
“…activity associated with poised and active enhancers and have been used to show that widespread changes in enhancer position and activity occur upon cell fate decisions such as the lineage commitment of pluripotent cells (Creyghton et al., 2010; Rada-Iglesias et al., 2011; Zentner et al., 2011).”
BackgroundHeintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · cited 1× · see citing works
“The definition of chromatin signatures has enabled the genome-wide identification of enhancer elements across multiple human cell types (ENCODE Project Consortium, 2012; Heintzman et al., 2007, 2009; Pennacchio et al., 2006; Rada-Iglesias et al., 2011; Kundaje et al., 2015).”
BackgroundSpatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895 · cited 1× · see citing works
“We assessed their localisation with respect to higher order features of chromosome architecture including TADs and Insulated Neighborhoods (INs) (Dixon et al., 2012; Ji et al., 2016; Nora et al., 2012; Sexton et al., 2012).”
MethodHistone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533 · cited 1× · see citing works
“The definition of chromatin signatures has enabled the genome-wide identification of enhancer elements across multiple human cell types (ENCODE Project Consortium, 2012; Heintzman et al., 2007, 2009; Pennacchio et al., 2006; Rada-Iglesias et al., 2011; Kundaje et al., 2015).”
BackgroundChromHMM: automating chromatin-state discovery and characterization
Ernst, J., & Kellis, M. (2012) · Nature Methods · doi:10.1038/nmeth.1906 · Cited by 2,489 · cited 5× · see citing works
“We used ChromHMM (Ernst and Kellis, 2012) to integrate these histone marks and to define four combinatorial chromatin states in both ESCs and NECs, as follows: active (characterised by H3K4me3 and/or H3K27ac); Polycomb-associated (H3K27me3); poised (H3K4 methylation and H3K27me3); and background…”
MethodInfluentialA unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233 · cited 1× · see citing works
“However, a regulatory function for some ‘unmarked’ PIRs also cannot be ruled out as recent mutagenesis experiments have identified functional elements that lack ’classic’ chromatin annotations (Pradeepa et al., 2016; Rajagopal et al., 2016).”
BackgroundTranscription factors: from enhancer binding to developmental control
Spitz, F., & Furlong, E. E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3207 · Cited by 2,227 · see citing works
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983 · cited 1× · see citing works
“We assessed their localisation with respect to higher order features of chromosome architecture including TADs and Insulated Neighborhoods (INs) (Dixon et al., 2012; Ji et al., 2016; Nora et al., 2012; Sexton et al., 2012).”
MethodChromatin architecture reorganization during stem cell differentiation
Dixon, J. R., Jung, I., Selvaraj, S., Shen, Y., Antosiewicz-Bourget, J. E., Lee, A. Y., Ye, Z., Kim, A., Rajagopal, N., Xie, W., et al. (2015) · Nature · doi:10.1038/nature14222 · Cited by 1,646 · cited 2× · see citing works
“These TAD definitions were used to compute the fraction of signifi- cant PCHi-C interactions falling inside TADs, alongside TADs reported by Dixon et al., 2015.”
BackgroundMethodThe long-range interaction landscape of gene promoters
Sanyal, A., Lajoie, B. R., Jain, G., & Dekker, J. (2012) · Nature · doi:10.1038/nature11279 · Cited by 1,489 · cited 5× · see citing works
“…the whole dataset, we found a significant concordance between the chro- matin states at promoters and their PIRs (Figure 1D), which is in line with previous studies in other human cell types (Jin et al., 2013; Mifsud et al., 2015; Sanyal et al., 2012) and provides validation of our dataset.”
BackgroundResultInfluentialModification of Enhancer Chromatin: What, How, and Why?
Calo, E., & Wysocka, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.038 · Cited by 1,457 · cited 1× · see citing works
“…decisions are associated with profound changes in chromatin organisation, which underlie the activation of lineage-specific and the silencing of lineage-inappropriate genes (Buecker and Wysocka, 2012; Bulger and Groudine, 2010; Calo and Wysocka, 2013; Hallikas et al., 2006; Ong and Corces, 2012).”
BackgroundIterative correction of Hi-C data reveals hallmarks of chromosome organization
Imakaev, M., Fudenberg, G., McCord, R. P., Naumova, N., Goloborodko, A., Lajoie, B. R., Dekker, J., & Mirny, L. A. (2012) · Nature Methods · doi:10.1038/nmeth.2148 · Cited by 1,423 · cited 1× · see citing works
“Coverage- and distance-related correction factors of the binned data were computed at 25 kb and 250 kb resolutions, based on the iterative correction algorithm (Imakaev et al., 2012).”
MethodTranscriptional enhancers: from properties to genome-wide predictions
Shlyueva, D., Stampfel, G., & Stark, A. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3682 · Cited by 1,356 · cited 3× · see citing works
“It is gener- ally accepted that this long-range action is facilitated by DNA-looping interactions (Pennacchio et al., 2013; Shlyueva et al., 2014).”
BackgroundLooping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00781-5 · Cited by 1,344 · cited 1× · see citing works
“Finally, there is also a possibility that multiple enhancers are jointly engaged in ‘chromatin hubs’ with promoters, rather than acting individually (Hanscombe et al., 1991; Jiang et al., 2016; Patrinos et al., 2004; Tolhuis et al., 2002; Wijgerde et al., 1995).”
BackgroundA high-resolution map of the three-dimensional chromatin interactome in human cells
Jin, F., Li, Y., Dixon, J. R., Selvaraj, S., Ye, Z., Lee, A. Y., Yen, C.-A., Schmitt, A. D., Espinoza, C. A., & Ren, B. (2013) · Nature · doi:10.1038/nature12644 · Cited by 1,208 · cited 3× · see citing works
“PIRs were also significantly enriched for sites bound by the architectural protein CTCF (Figure 1—figure supplement 2B; based on ENCODE data available for ESCs only), consistent with previous observations in other cell types (Jin et al., 2013; Phillips-Cremins et al., 2013; Sanyal et al., 2012).”
BackgroundResultArchitectural protein subclasses shape 3D organization of genomes during lineage commitment
Phillips-Cremins, J. E., Sauria, M. E. G., Sanyal, A., Gerasimova, T. I., Lajoie, B. R., Bell, J. S. K., Ong, C.-T., Hookway, T. A., Guo, C., Sun, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.053 · Cited by 1,187 · cited 2× · see citing works
“…studies provided evidence of interactions associated with transcriptional changes upon line- age commitment (Denholtz et al., 2013; Kieffer-Kwon et al., 2013; Phillips-Cremins et al., 2013; eLife digest Virtually every cell in the body contains the same set of DNA, which encodes thousands of genes.”
BackgroundResultIn vivo enhancer analysis of human conserved non-coding sequences
Pennacchio, L. A., Ahituv, N., Moses, A. M., Prabhakar, S., Nobrega, M. A., Shoukry, M., Minovitsky, S., Dubchak, I., Holt, A., Lewis, K. D., et al. (2006) · Nature · doi:10.1038/nature05295 · Cited by 1,165 · cited 2× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundGenome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq
Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A. (2013) · Science · doi:10.1126/science.1232542 · Cited by 1,125 · cited 1× · see citing works
“…15 of 26 Theoretically, the generally independent enhancer action also enables activation signals from individual elements to quantitatively ‘add up’ (at least to some extent) to promote stronger transcrip- tional outputs (Arnold et al., 2013; Bothma et al., 2015; Lam et al., 2015; Spivakov, 2014).”
BackgroundVISTA Enhancer Browser—a database of tissue-specific human enhancers
Visel, A., Minovitsky, S., Dubchak, I., & Pennacchio, L. A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl822 · Cited by 1,080 · cited 5× · see citing works
“Embryo reporter assays and enhancer activity patterns are from the VISTA Enhancer Browser (Visel et al., 2007).”
BackgroundMethodInfluentialExploring the three-dimensional organization of genomes: Interpreting chromatin interaction data
Dekker, J., Marti-Renom, M. A., & Mirny, L. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3454 · Cited by 1,068 · cited 1× · see citing works
“Over the last decade, chromosome conformation capture (3C) and derived methods have enabled the biochemical mapping of looping interactions to offer new insights into their architecture across different cell types (Dekker et al., 2013; de Laat and Duboule, 2013; Schmitt et al., 2016).”
BackgroundMapping long-range promoter contacts in human cells with high-resolution capture Hi-C
Mifsud, B., Tavares-Cadete, F., Young, A. N., Sugar, R., Schoenfelder, S., Ferreira, L., Wingett, S. W., Andrews, S., Grey, W., Ewels, P. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3286 · Cited by 990 · cited 4× · see citing works
“…to enrich Hi-C libraries for interactions involving the promoters of most annotated genes, providing a global view on promoter interactions that is independent of the activity of interacting regions and identity of proteins recruited to them (Mifsud et al., 2015; Schoenfelder et al., 2015a).”
BackgroundMethodResultInfluentialSelf-citationTranscriptional regulation by Polycomb group proteins
Di Croce, L., & Helin, K. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2669 · Cited by 864 · see citing works
HiCUP: pipeline for mapping and processing Hi-C data
Wingett, S., Ewels, P., Furlan-Magaril, M., Nagano, T., Schoenfelder, S., Fraser, P., & Andrews, S. (2015) · F1000Research · doi:10.12688/f1000research.7334.1 · Cited by 724 · cited 1× · see citing works
“Hi-C analysis and the definition of TADs, TAD boundaries and compartments Raw sequencing reads were processed using the HiCUP pipeline (Wingett et al., 2015), which mapped sequencing read pairs against the human genome (GRCh37), filtered out experimental arti- facts such as circularized reads and…”
MethodSelf-citationEnhancer Control of Transcriptional Bursting
Fukaya, T., Lim, B., & Levine, M. (2016) · Cell · doi:10.1016/j.cell.2016.05.025 · Cited by 721 · cited 3× · see citing works
“The emerging studies at the single-molecule level (such as [Bartman et al., 2016; Fukaya et al., 2016]) will likely shed further light on the molecular mechanisms that underpin the principles of CRU organisation.”
BackgroundEnhancers: five essential questions
Pennacchio, L. A., Bickmore, W. A., Dean, A., Nóbrega, M. A., & Bejerano, G. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3458 · Cited by 584 · cited 2× · see citing works
“It is gener- ally accepted that this long-range action is facilitated by DNA-looping interactions (Pennacchio et al., 2013; Shlyueva et al., 2014).”
BackgroundEpigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions
Zentner, G. E., Tesar, P. J., & Scacheri, P. C. (2011) · Genome Research · doi:10.1101/gr.122382.111 · Cited by 564 · cited 1× · see citing works
“…activity associated with poised and active enhancers and have been used to show that widespread changes in enhancer position and activity occur upon cell fate decisions such as the lineage commitment of pluripotent cells (Creyghton et al., 2010; Rada-Iglesias et al., 2011; Zentner et al., 2011).”
BackgroundEnhancer loops appear stable during development and are associated with paused polymerase
Ghavi-Helm, Y., Klein, F. A., Pakozdi, T., Ciglar, L., Noordermeer, D., Huber, W., & Furlong, E. E. M. (2014) · Nature · doi:10.1038/nature13417 · Cited by 536 · see citing works
Topology of mammalian developmental enhancers and their regulatory landscapes
de Laat, W., & Duboule, D. (2013) · Nature · doi:10.1038/nature12753 · Cited by 521 · see citing works
Shadow enhancers as a source of evolutionary novelty
Hong, J.-W., Hendrix, D. A., & Levine, M. S. (2008) · Science · doi:10.1126/science.1160631 · Cited by 474 · cited 4× · see citing works
“…gene regulation by multiple enhancers The CRU view provides an opportunity to consider multi-modular gene regulation in early human development that has hitherto been studied on a limited number of genes, predominantly in model organisms (Barolo, 2012; Cannavò et al., 2016; Hong et al., 2008).”
BackgroundInfluentialTranscription complex stability and chromatin dynamics in vivo
Wijgerde, M., Grosveld, F. G., & Fraser, P. (1995) · Nature · doi:10.1038/377209a0 · Cited by 471 · cited 1× · see citing works
“Finally, there is also a possibility that multiple enhancers are jointly engaged in ‘chromatin hubs’ with promoters, rather than acting individually (Hanscombe et al., 1991; Jiang et al., 2016; Patrinos et al., 2004; Tolhuis et al., 2002; Wijgerde et al., 1995).”
BackgroundSelf-citationA Global Control Region Defines a Chromosomal Regulatory Landscape Containing the HoxD Cluster
Spitz, F., Gonzãlez, F., & Duboule, D. (2003) · Cell · doi:10.1016/s0092-8674(03)00310-6 · Cited by 466 · cited 1× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundHallikas, O. K., Palin, K., Sinjushina, N., Rautiainen, R., Partanen, J. M., Ukkonen, E., & Taipale, J. (2006) · Cell · doi:10.1016/j.cell.2005.10.042 · Cited by 465 · see citing works
The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Schoenfelder, S., Furlan-Magaril, M., Mifsud, B., Tavares-Cadete, F., Sugar, R., Javierre, B.-M., Nagano, T., Katsman, Y., Sakthidevi, M., Wingett, S. W., et al. (2015) · Genome Research · doi:10.1101/gr.185272.114 · Cited by 460 · see citing works
Self-citationEnhancer-promoter interactions are encoded by complex genomic signatures on looping chromatin
Whalen, S., Truty, R. M., & Pollard, K. S. (2016) · Nature Genetics · doi:10.1038/ng.3539 · Cited by 456 · cited 1× · see citing works
“…specific determinants of chromosomal interactions are still not fully understood, which presents challenges for the high-confidence predic- tion of regulatory interactions from sequence and epigenetic information (Mora et al., 2016; Roy et al., 2015; Shlyueva et al., 2014; Whalen et al., 2016).”
BackgroundTranscriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Gifford, C. A., Ziller, M. J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A. K., Kelley, D. R., Shishkin, A. A., Issner, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.037 · Cited by 435 · see citing works
CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data
Cairns, J., Freire-Pritchett, P., Wingett, S. W., Várnai, C., Dimond, A., Plagnol, V., Zerbino, D., Schoenfelder, S., Javierre, B.-M., Osborne, C., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-0992-2 · Cited by 417 · cited 2× · see citing works
“PCHi-C data normalisation and signal detection using the CHiCAGO pipeline (Cairns et al., 2016) identified 75,795 significant cis-interactions between promoters and other genomic regions in ESCs and 75,624 in NECs.”
MethodInfluentialSelf-citation3D Chromosome Regulatory Landscape of Human Pluripotent Cells
Ji, X., Dadon, D. B., Powell, B. E., Fan, Z. P., Borges-Rivera, D., Shachar, S., Weintraub, A. S., Hnisz, D., Pegoraro, G., Lee, T. I., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2015.11.007 · Cited by 400 · cited 4× · see citing works
“For INs, we used the published genomic coordinates (available for ESCs only) that were defined on the basis of cohesin ChIA-PET and CTCF-binding data (Ji et al., 2016).”
BackgroundMethodInfluentialPolycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Schoenfelder, S., Sugar, R., Dimond, A., Javierre, B.-M., Armstrong, H., Mifsud, B., Dimitrova, E., Matheson, L., Tavares-Cadete, F., Furlan-Magaril, M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3393 · Cited by 398 · cited 1× · see citing works
“We assessed their localisation with respect to higher order features of chromosome architecture including TADs and Insulated Neighborhoods (INs) (Dixon et al., 2012; Ji et al., 2016; Nora et al., 2012; Sexton et al., 2012).”
MethodSelf-citationShadow Enhancers Foster Robustness of Drosophila Gastrulation
Perry, M. W., Boettiger, A. N., Bothma, J. P., & Levine, M. (2010) · Current Biology · doi:10.1016/j.cub.2010.07.043 · Cited by 396 · cited 1× · see citing works
“…been suggested that this cis-regulatory organisation ensures the robustness of gene regulation and can buffer the effects of deleterious sequence variation, as well as providing opportunities for evolutionary innovation (Barolo, 2012; Cannavò et al., 2016; Hong et al., 2008; Perry et al., 2010).”
BackgroundEpigenetic signatures of stem-cell identity
Spivakov, M., & Fisher, A. G. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2046 · Cited by 382 · see citing works
Self-citationSagai, T., Hosoya, M., Mizushina, Y., Tamura, M., & Shiroishi, T. (2005) · Development · doi:10.1242/dev.01613 · Cited by 379 · cited 1× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundFraser, J., Ferrai, C., Chiariello, A. M., Schueler, M., Rito, T., Laudanno, G., Barbieri, M., Moore, B. L., Kraemer, D., Aitken, S., et al. (2015) · Molecular Systems Biology · doi:10.15252/msb.20156492 · Cited by 356 · see citing works
Enhancer Regulation of Transcriptional Bursting Parameters Revealed by Forced Chromatin Looping
Bartman, C. R., Hsu, S. C., Hsiung, C. C.-S., Raj, A., & Blobel, G. A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.007 · Cited by 345 · cited 2× · see citing works
“The emerging studies at the single-molecule level (such as [Bartman et al., 2016; Fukaya et al., 2016]) will likely shed further light on the molecular mechanisms that underpin the principles of CRU organisation.”
BackgroundGenome-wide mapping and analysis of chromosome architecture
Schmitt, A. D., Hu, M., & Ren, B. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.104 · Cited by 344 · cited 1× · see citing works
“Over the last decade, chromosome conformation capture (3C) and derived methods have enabled the biochemical mapping of looping interactions to offer new insights into their architecture across different cell types (Dekker et al., 2013; de Laat and Duboule, 2013; Schmitt et al., 2016).”
BackgroundKieffer-Kwon, K.-R., Tang, Z., Mathé, E. A., Qian, J., Sung, M., Li, G., Resch, W., Baek, S., Pruett, N. D., Grøntved, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.039 · Cited by 326 · cited 1× · see citing works
“These studies provided evidence of interactions associated with transcriptional changes upon line- age commitment (Denholtz et al., 2013; Kieffer-Kwon et al., 2013; Phillips-Cremins et al., 2013; eLife digest Virtually every cell in the body contains the same set of DNA, which encodes thousands of…”
BackgroundLi, L., Lyu, X., Hou, C., Takenaka, N., Nguyen, H. Q., Ong, C., Cubeñas-Potts, C., Hu, M., Lei, E. P., Bosco, G., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.023 · Cited by 315 · cited 2× · see citing works
“…bound by specific proteins (such as cohesin and RNA polymerase II) have made it possible to detect subsets of promoter-enhancer interactions at high resolution (Heidari et al., 2014; Li et al., 2015; Sanyal et al., 2012) and delineate their dynamics during cell differentiation and reprogramming.”
BackgroundEnhancers as information integration hubs in development: lessons from genomics
Buecker, C., & Wysocka, J. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.02.008 · Cited by 286 · cited 1× · see citing works
“…decisions are associated with profound changes in chromatin organisation, which underlie the activation of lineage-specific and the silencing of lineage-inappropriate genes (Buecker and Wysocka, 2012; Bulger and Groudine, 2010; Calo and Wysocka, 2013; Hallikas et al., 2006; Ong and Corces, 2012).”
BackgroundImportance of globin gene order for correct developmental expression.Preprint
Hanscombe, O., Whyatt, D., Fraser, P., Yannoutsos, N., Greaves, D. R., Dillon, N., & Grosveld, F. G. (1991) · Genes & Development · doi:10.1101/gad.5.8.1387 · Cited by 283 · see citing works
Self-citationGenome-wide map of regulatory interactions in the human genome
Heidari, N., Phanstiel, D. H., He, C., Grubert, F., Jahanbani, F., Kasowski, M., Zhang, M. Q., & Snyder, M. P. (2014) · Genome Research · doi:10.1101/gr.176586.114 · Cited by 278 · cited 1× · see citing works
“…bound by specific proteins (such as cohesin and RNA polymerase II) have made it possible to detect subsets of promoter-enhancer interactions at high resolution (Heidari et al., 2014; Li et al., 2015; Sanyal et al., 2012) and delineate their dynamics during cell differentiation and reprogramming.”
BackgroundDenholtz, M., Bonora, G., Chronis, C., Splinter, E., de Laat, W., Ernst, J., Pellegrini, M., & Plath, K. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.08.013 · Cited by 274 · cited 2× · see citing works
“These studies provided evidence of interactions associated with transcriptional changes upon line- age commitment (Denholtz et al., 2013; Kieffer-Kwon et al., 2013; Phillips-Cremins et al., 2013; eLife digest Virtually every cell in the body contains the same set of DNA, which encodes thousands of…”
BackgroundHistone H3 globular domain acetylation identifies a new class of enhancers
Pradeepa, M. M., Grimes, G. R., Kumar, Y., Olley, G., Taylor, G. C. A., Schneider, R., & Bickmore, W. A. (2016) · Nature Genetics · doi:10.1038/ng.3550 · Cited by 240 · cited 1× · see citing works
“However, a regulatory function for some ‘unmarked’ PIRs also cannot be ruled out as recent mutagenesis experiments have identified functional elements that lack ’classic’ chromatin annotations (Pradeepa et al., 2016; Rajagopal et al., 2016).”
BackgroundHigh-throughput mapping of regulatory DNA
Rajagopal, N., Srinivasan, S., Kooshesh, K., Guo, Y., Edwards, M. D., Banerjee, B., Syed, T., Emons, B. J. M., Gifford, D. K., & Sherwood, R. I. (2016) · Nature Biotechnology · doi:10.1038/nbt.3468 · Cited by 238 · cited 1× · see citing works
“However, a regulatory function for some ‘unmarked’ PIRs also cannot be ruled out as recent mutagenesis experiments have identified functional elements that lack ’classic’ chromatin annotations (Pradeepa et al., 2016; Rajagopal et al., 2016).”
BackgroundShadow Enhancers Are Pervasive Features of Developmental Regulatory Networks
Cannavò, E., Khoueiry, P., Garfield, D. A., Geeleher, P., Zichner, T., Gustafson, E. H., Ciglar, L., Korbel, J. O., & Furlong, E. E. M. (2016) · Current Biology · doi:10.1016/j.cub.2015.11.034 · Cited by 235 · cited 2× · see citing works
“…gene regulation by multiple enhancers The CRU view provides an opportunity to consider multi-modular gene regulation in early human development that has hitherto been studied on a limited number of genes, predominantly in model organisms (Barolo, 2012; Cannavò et al., 2016; Hong et al., 2008).”
BackgroundJeong, Y., El-Jaick, K. B., Roessler, E., Muenke, M., & Epstein, D. J. (2006) · Development · doi:10.1242/dev.02239 · Cited by 227 · cited 1× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundApostolou, E., Ferrari, F., Walsh, R. M., Bar‐Nur, O., Stadtfeld, M., Cheloufi, S., Stuart, H. T., Polo, J. M., Ohsumi, T. K., Borowsky, M. L., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.04.013 · Cited by 215 · cited 2× · see citing works
“Examples of instructive and permissive interactions have been described in pluripotent cell reprogramming and differentiation (Apostolou et al., 2013; Denholtz et al., 2013; Phillips- Cremins et al., 2013; Wei et al., 2013; Zhang et al., 2013), but little was known on a global scale about which…”
BackgroundInfluentialWei, Z., Gao, F., Kim, S., Yang, H., Lyu, J., An, W., Wang, K., & Lu, W. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.05.010 · Cited by 207 · cited 2× · see citing works
“DOI: 10.7554/eLife.21926 2 of 26 Zhang et al., 2013), as well as revealed interactions formed in anticipation of changes in gene activity (Apostolou et al., 2013; Ghavi-Helm et al., 2014; Wei et al., 2013).”
BackgroundInfluentialEnhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo
Bothma, J. P., Garcia, H. G., Ng, S., Perry, M. W., Gregor, T., & Levine, M. (2015) · eLife · doi:10.7554/elife.07956 · Cited by 192 · cited 2× · see citing works
“However, analyses in Drosophila have identified exceptions to additive enhancer activity (Bothma et al., 2015) and have provided exam- ples of enhancers that activate more than one promoter in a coordinated fashion (Fukaya et al., 2016), which is not immediately expected from the ‘hit-and-run’…”
BackgroundEnhancers: The abundance and function of regulatory sequences beyond promoters
Bulger, M., & Groudine, M. T. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.11.035 · Cited by 187 · cited 1× · see citing works
“…decisions are associated with profound changes in chromatin organisation, which underlie the activation of lineage-specific and the silencing of lineage-inappropriate genes (Buecker and Wysocka, 2012; Bulger and Groudine, 2010; Calo and Wysocka, 2013; Hallikas et al., 2006; Ong and Corces, 2012).”
BackgroundMultiple interactions between regulatory regions are required to stabilize an active chromatin hub
Patrinos, G. P., de Krom, M., de Boer, E., Langeveld, A., Imam, A. M. A., Strouboulis, J., de Laat, W., & Grosveld, F. G. (2004) · Genes & Development · doi:10.1101/gad.289704 · Cited by 170 · cited 1× · see citing works
“Finally, there is also a possibility that multiple enhancers are jointly engaged in ‘chromatin hubs’ with promoters, rather than acting individually (Hanscombe et al., 1991; Jiang et al., 2016; Patrinos et al., 2004; Tolhuis et al., 2002; Wijgerde et al., 1995).”
BackgroundCarvajal, J. J., Cox, D., Summerbell, D., & Rigby, P. W. J. (2001) · Development · doi:10.1242/dev.128.10.1857 · Cited by 162 · see citing works
EMAGE mouse embryo spatial gene expression database: 2014 update
Richardson, L., Venkataraman, S., Stevenson, P. L., Yang, Y., Moss, J. E., Graham, L., Burton, N., Hill, B., Rao, J., Baldock, R., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1155 · Cited by 161 · cited 1× · see citing works
“5 mouse embryo (EMAGE gene expression database; EMAGE:1689; [Richardson et al., 2014]) broadly matches the combined tissue-restricted pattern of its enhancers.”
BackgroundRuf, S., Symmons, O., Uslu, V. V., Dolle, D. D., Hot, C., Ettwiller, L. M., & Spitz, F. (2011) · Nature Genetics · doi:10.1038/ng.790 · Cited by 157 · cited 1× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundClustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
Vieux-Rochas, M., Fabre, P. J., Leleu, M., Duboule, D., & Noordermeer, D. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504783112 · Cited by 156 · cited 1× · see citing works
“…connectivity to regions associated with Polycomb-mediated repression and poising, reinforcing the role of Polycomb-group proteins in controlling chromosomal topology at transcriptionally inactive genes (Entrevan et al., 2016; Li et al., 2015; Schoenfelder et al., 2015b; Vieux-Rochas et al., 2015).”
BackgroundMechanisms of transcriptional precision in animal development
Lagha, M., Bothma, J. P., & Levine, M. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.03.006 · Cited by 145 · cited 1× · see citing works
“…(potentially at both single-state and dual-state CRUs) that is consistent with the ‘hit-and-run’ model of transcrip- tional regulation (Schaffner, 1988; Varala et al., 2015), and provides a flexible way to fine-tune the expression of multi-enhancer genes (Guerrero et al., 2010; Lagha et al., 2012).”
ResultEnhancers: emerging roles in cell fate specification
Ong, C., & Corces, V. G. (2012) · The EMBO Reports · doi:10.1038/embor.2012.52 · Cited by 144 · see citing works
Marinić, M., Aktaş, T., Ruf, S., & Spitz, F. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.01.025 · Cited by 142 · cited 1× · see citing works
“…1 of 26 Cis-regulatory elements are often considerable distances away from their target gene promoters and may not control their nearest genes (Carvajal et al., 2001; Jeong et al., 2006; Marinić et al., 2013; Pennacchio et al., 2006; Ruf et al., 2011; Sagai et al., 2005; Spitz et al., 2003).”
BackgroundBarolo, S. (2012) · BioEssays · doi:10.1002/bies.201100121 · Cited by 136 · cited 3× · see citing works
“…gene regulation by multiple enhancers The CRU view provides an opportunity to consider multi-modular gene regulation in early human development that has hitherto been studied on a limited number of genes, predominantly in model organisms (Barolo, 2012; Cannavò et al., 2016; Hong et al., 2008).”
BackgroundZhang, H., Jiao, W., Sun, L., Fan, J., Chen, M., Wang, H., Xu, X., Shen, A., Li, T., Niu, B., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.05.012 · Cited by 130 · cited 2× · see citing works
“DOI: 10.7554/eLife.21926 2 of 26 Zhang et al., 2013), as well as revealed interactions formed in anticipation of changes in gene activity (Apostolou et al., 2013; Ghavi-Helm et al., 2014; Wei et al., 2013).”
BackgroundInfluentialA predictive modeling approach for cell line-specific long-range regulatory interactions
Roy, S., Siahpirani, A. F., Chasman, D. A., Knaack, S., Ay, F., Stewart, R. M., Wilson, M. D., & Sridharan, R. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv865 · Cited by 121 · cited 1× · see citing works
“…specific determinants of chromosomal interactions are still not fully understood, which presents challenges for the high-confidence predic- tion of regulatory interactions from sequence and epigenetic information (Mora et al., 2016; Roy et al., 2015; Shlyueva et al., 2014; Whalen et al., 2016).”
BackgroundLam, D. D., de Souza, F. S. J., Nasif, S., Yamashita, M., López‐Leal, R., Otero-Corchón, V., Meece, K., Sampath, H., Mercer, A. J., Wardlaw, S. L., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004935 · Cited by 115 · cited 1× · see citing works
“…15 of 26 Theoretically, the generally independent enhancer action also enables activation signals from individual elements to quantitatively ‘add up’ (at least to some extent) to promote stronger transcrip- tional outputs (Arnold et al., 2013; Bothma et al., 2015; Lam et al., 2015; Spivakov, 2014).”
BackgroundIn the loop: promoter–enhancer interactions and bioinformatics
Mora, A., Sandve, G. K., Gabrielsen, O. S., & Eskeland, R. (2015) · Briefings in Bioinformatics · doi:10.1093/bib/bbv097 · Cited by 115 · cited 1× · see citing works
“…specific determinants of chromosomal interactions are still not fully understood, which presents challenges for the high-confidence predic- tion of regulatory interactions from sequence and epigenetic information (Mora et al., 2016; Roy et al., 2015; Shlyueva et al., 2014; Whalen et al., 2016).”
BackgroundCis-regulatory mutations in human disease
Epstein, D. J. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp021 · Cited by 113 · cited 1× · see citing works
“Promoter – enhancer interactions are vitally important for gene regulation and their disruption may lead to pronounced developmental abnormalities (Epstein, 2009).”
BackgroundRegulation of Genome Architecture and Function by Polycomb Proteins
Entrevan, M., Schuettengruber, B., & Cavalli, G. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.04.009 · Cited by 109 · see citing works
Spurious transcription factor binding: Non‐functional or genetically redundant?
Spivakov, M. (2014) · BioEssays · doi:10.1002/bies.201400036 · Cited by 96 · cited 1× · see citing works
“…15 of 26 Theoretically, the generally independent enhancer action also enables activation signals from individual elements to quantitatively ‘add up’ (at least to some extent) to promote stronger transcrip- tional outputs (Arnold et al., 2013; Bothma et al., 2015; Lam et al., 2015; Spivakov, 2014).”
BackgroundSelf-citationA hit-and-run mechanism for transcriptional activation?
Schaffner, W. (1988) · Nature · doi:10.1038/336427a0 · Cited by 52 · cited 1× · see citing works
“Over the last decade, chromosome conformation capture (3C) and derived methods have enabled the biochemical mapping of looping interactions to offer new insights into their architecture across different cell types (Dekker et al., 2013; de Laat and Duboule, 2013; Schmitt et al., 2016).”
BackgroundJiang, T., Raviram, R., Snetkova, V., Rocha, P. P., Proudhon, C., Badri, S., Bonneau, R., Skok, J. A., & Kluger, Y. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw568 · Cited by 48 · cited 1× · see citing works
“Finally, there is also a possibility that multiple enhancers are jointly engaged in ‘chromatin hubs’ with promoters, rather than acting individually (Hanscombe et al., 1991; Jiang et al., 2016; Patrinos et al., 2004; Tolhuis et al., 2002; Wijgerde et al., 1995).”
BackgroundTranscriptional enhancers: functional insights and role in human disease
Miguel-Escalada, I., Pasquali, L., & Ferrer, J. P. (2015) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2015.08.009 · Cited by 39 · cited 1× · see citing works
“Furthermore, while it is generally accepted that many genes are controlled by multiple regulatory elements (Barolo, 2012; Miguel-Escalada et al., 2015) our understanding of multi-modular gene regulation remains limited, particularly in the context of mammalian development and stem cell…”
BackgroundMolecular stages of rapid and uniform neuralization of human embryonic stem cells
Bajpai, R., Coppola, G., Kaul, M., Talantova, M. V., Cimadamore, F., Nilbratt, M., Geschwind, D. H., Lipton, S. A., & Terskikh, A. V. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.18 · Cited by 36 · cited 1× · see citing works
“Here, we use PCHi-C in human embryonic stem cells (ESCs) and ESC-derived neuroectodermal cells (NECs) (Bajpai et al., 2009) to create a high-resolution resource of promoter contacts and their dynamics during early lineage commitment in the context of extensive chromatin changes that occur at the…”
MethodSecondary enhancers synergise with primary enhancers to guarantee fine-tuned muscle gene expression
Guerrero, L., Marco-Ferreres, R., Serrano, A. L., Arredondo, J. J., & Cervera, M. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.10.006 · Cited by 29 · see citing works
“Hit‐and‐Run” leaves its mark: Catalyst transcription factors and chromatin modification
Varala, K., Li, Y., Marshall‐Colón, A., Para, A., & Coruzzi, G. M. (2015) · BioEssays · doi:10.1002/bies.201400205 · Cited by 22 · cited 1× · see citing works
“…(potentially at both single-state and dual-state CRUs) that is consistent with the ‘hit-and-run’ model of transcrip- tional regulation (Schaffner, 1988; Varala et al., 2015), and provides a flexible way to fine-tune the expression of multi-enhancer genes (Guerrero et al., 2010; Lagha et al., 2012).”
Result
Flagged first, then by citations
Cited by
Sorted by citations
Long-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102 · see citing works
Self-citationThe role of 3D genome organization in development and cell differentiation
Zheng, H., & Xie, W. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0132-4 · Cited by 711 · see citing works
A compendium of promoter-centered long-range chromatin interactions in the human genome
Jung, I., Schmitt, A., Diao, Y., Lee, A. J., Liu, T., Yang, D., Tan, C., Eom, J., Chan, M., Chee, S., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0494-8 · Cited by 362 · see citing works
The relationship between genome structure and function
Oudelaar, A. M., & Higgs, D. R. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00303-x · Cited by 304 · see citing works
Rubin, A. J., Barajas, B. C., Furlan-Magaril, M., Lopez-Pajares, V., Mumbach, M. R., Howard, I., Kim, D. S., Boxer, L. D., Cairns, J., Spivakov, M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3935 · Cited by 293 · see citing works
Self-citationEvaluating Enhancer Function and Transcription
Field, A. R., & Adelman, K. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011420-095916 · Cited by 218 · see citing works
“Consistent with this, studies using chromatin conformation capture (3C)-based methods have given a wide range of estimates, from 7% (22) to 46% (28), of enhancer elements that contact the closest gene.”
ResultChromatin three-dimensional interactions mediate genetic effects on gene expression
Delaneau, O., Zazhytska, M., Borel, C., Giannuzzi, G., Rey, G., Howald, C., Kumar, S., Ongen, H., Popadin, K., Marbach, D., et al. (2019) · Science · doi:10.1126/science.aat8266 · Cited by 168 · see citing works
“This hypothesis is in line with recent models of trans interactions (28, 35), phase separation (36, 37), and gene activation (38).”
ResultThe Bivalent Genome: Characterization, Structure, and Regulation
Blanco, E., González-Ramírez, M., Alcaine-Colet, A., Aranda, S., & Croce, L. D. (2019) · Trends in Genetics · doi:10.1016/j.tig.2019.11.004 · Cited by 215 · see citing works
Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis
Kragesteen, B. K., Spielmann, M., Paliou, C., Heinrich, V., Schöpflin, R., Esposito, A., Annunziatella, C., Bianco, S., Chiariello, A. M., Jerković, I., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0221-x · Cited by 183 · see citing works
Candidate silencer elements for the human and mouse genomes
Jayavelu, N. D., Jajodia, A., Mishra, A., & Hawkins, R. D. (2020) · Nature Communications · doi:10.1038/s41467-020-14853-5 · Cited by 180 · see citing works
Paliou, C., Guckelberger, P., Schöpflin, R., Heinrich, V., Esposito, A., Chiariello, A. M., Bianco, S., Annunziatella, C., Helmuth, J., Haas, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900672116 · Cited by 163 · see citing works
Thiecke, M. J., Wutz, G., Muhar, M., Tang, W., Bevan, S., Malysheva, V., Stocsits, R., Neumann, T., Zuber, J., Fraser, P., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107929 · Cited by 177 · see citing works
Self-citationRinzema, N. J., Sofiadis, K., Tjalsma, S. J. D., Verstegen, M. J. A. M., Oz, Y., Valdes-Quezada, C., Felder, A.-K., Filipovska, T., van der Elst, S., de Andrade dos Ramos, Z., et al. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00787-7 · Cited by 166 · see citing works
Promoter bivalency favors an open chromatin architecture in embryonic stem cells
Martín, G. M., Blanco, E., Ballaré, C., Sansó, M., Spill, Y. G., Hu, D., Aoi, Y., Dily, F. L., Shilatifard, A., Martı́-Renom, M. A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0218-5 · Cited by 148 · see citing works
Greenwald, W. W. Y., Li, H., Benaglio, P., Jakubosky, D. A., Matsui, H., Schmitt, A. D., Selvaraj, S., D’Antonio, M., D’Antonio‐Chronowska, A., Smith, E. N., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08940-5 · Cited by 134 · see citing works
A promoter interaction map for cardiovascular disease genetics
Montefiori, L. E., Sobreira, D. R., Sakabe, N. J., Aneas, I., Joslin, A. C., Hansen, G. T., Bozek, G., Moskowitz, I. P., McNally, E. M., & Nóbrega, M. A. (2018) · eLife · doi:10.7554/elife.35788 · Cited by 145 · see citing works
The three-dimensional genome: regulating gene expression during pluripotency and development
Andrey, G., & Mundlos, S. (2017) · Development · doi:10.1242/dev.148304 · Cited by 129 · see citing works
“…in a large-scale study of the promoter interactomes of PCs and neuroectodermal cells, around 50% of promoter-interacting regions were re-wired and 50% were retained between both cell types, arguing for extensive chromatin dynamics upon cell differentiation (Freire-Pritchett et al., 2017).”
BackgroundMethodSingle-cell measurement of higher-order 3D genome organization with scSPRITE
Arrastia, M. V., Jachowicz, J. W., Ollikainen, N., Curtis, M. S., Lai, C., Quinodoz, S. A., Selck, D. A., Ismagilov, R. F., & Guttman, M. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00998-1 · Cited by 126 · see citing works
G-quadruplex DNA structures in human stem cells and differentiation
Zyner, K. G., Simeone, A., Flynn, S. M., Doyle, C., Marsico, G., Adhikari, S., Portella, G., Tannahill, D., & Balasubramanian, S. (2022) · Nature Communications · doi:10.1038/s41467-021-27719-1 · Cited by 122 · see citing works
Dynamics of the 4D Genome during in Vivo Lineage Specification and Differentiation
Oudelaar, A. M., Beagrie, R. A., Gosden, M., de Ornellas, S., Georgiades, E., Kerry, J., Hidalgo, D., Carrelha, J., Shivalingam, A., El-Sagheer, A. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16598-7 · Cited by 119 · see citing works
Novo, C. L., Javierre, B.-M., Cairns, J., Segonds-Pichon, A., Wingett, S. W., Freire-Pritchett, P., Furlan-Magaril, M., Schoenfelder, S., Fraser, P., & Rugg-Gunn, P. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.040 · Cited by 119 · see citing works
“In contrast, intra-TAD DNA loops are typically cell-type specific and are frequently rewired upon cell state changes (Smith et al., 2016; Denholtz et al., 2013; Schoenfelder et al., 2015b; Freire-Pritchett et al., 2017).”
BackgroundSelf-citationPromoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Schoenfelder, S., Javierre, B. M., Furlan-Magaril, M., Wingett, S., & Fraser, P. (2018) · Journal of Visualized Experiments · doi:10.3791/57320 · Cited by 114 · see citing works
Self-citationMadsen, J. G. S., Madsen, M. S., Rauch, A., Traynor, S., Hauwaert, E. L. V., Haakonsson, A. K., Javierre, B. M., Hyldahl, M., Fraser, P., & Mandrup, S. (2020) · Nature Genetics · doi:10.1038/s41588-020-0709-z · Cited by 94 · see citing works
Self-citationNucleome Dynamics during Retinal Development
Norrie, J. L., Lupo, M. S., Xu, B., Aldiri, I., Valentine, M. B., Putnam, D. K., Griffiths, L. M., Zhang, J., Johnson, D. A., Easton, J. B., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.002 · Cited by 87 · see citing works
Increased enhancer–promoter interactions during developmental enhancer activation in mammals
Chen, Z., Snetkova, V., Bower, G., Jacinto, S. H., Clock, B., Dizehchi, A., Barozzi, I., Mannion, B. J., Alcaina‐Caro, A., López-Rı́os, J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01681-2 · Cited by 84 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Self-citationHiCAR is a robust and sensitive method to analyze open-chromatin-associated genome organization
Wei, X., Yu, X., Peters, D., Marius, C., Sun, T., Shan, R., Ou, J., Lin, X., Yue, F., Li, W., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.01.023 · Cited by 83 · see citing works
Three-dimensional genome architecture and emerging technologies: looping in disease
Mishra, A., & Hawkins, R. D. (2017) · Genome Medicine · doi:10.1186/s13073-017-0477-2 · Cited by 77 · see citing works
“Integrating 3D genomic data with genetic data and applying polymer modeling approaches with Hi-C catalogues may recapitulate architectural effects of disease variants [8, 43, 44] and can serve as reference 3D genome maps for clinically relevant samples—useful for generating testable hypotheses toward therapeutic oppor…”
BackgroundChoy, M., Javierre, B. M., Williams, S. G., Baross, S. L., Liu, Y., Wingett, S., Akbarov, A., Wallace, C., Freire-Pritchett, P., Rugg‐Gunn, P. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04931-0 · Cited by 72 · see citing works
Self-citationThe interdependence of gene-regulatory elements and the 3D genome
Vermunt, M. W., Zhang, D., & Blobel, G. A. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201809040 · Cited by 65 · see citing works
Interpreting the impact of noncoding structural variation in neurodevelopmental disorders
D’haene, E., & Vergult, S. (2020) · Genetics in Medicine · doi:10.1038/s41436-020-00974-1 · Cited by 60 · see citing works
Zhang, S., Bell, E., Zhi, H., Brown, S., Imran, S. A. M., Azuara, V., & Cui, W. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1228-7 · Cited by 59 · see citing works
“moter Capture Hi-C analysis as an enhancer region of POU3F2, which exhibited regulation on reporter gene expression in the CNS of mouse embryos [48].”
BackgroundSchoenfelder, S., Mifsud, B., Senner, C. E., Todd, C. D., Chrysanthou, S., Darbo, E., Hemberger, M., & Branco, M. R. (2018) · Nature Communications · doi:10.1038/s41467-018-06666-4 · Cited by 54 · see citing works
Self-citationWatt, S., Vasquez, L., Walter, K., Mann, A. L., Kundu, K., Chen, L., Sims, Y., Ecker, S., Burden, F., Farrow, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22548-8 · Cited by 63 · see citing works
Self-citationChromatin architecture reorganization during neuronal cell differentiation in Drosophila genomePreprint
Chathoth, K. T., & Zabet, N. R. (2019) · Genome Research · doi:10.1101/gr.246710.118 · Cited by 54 · see citing works
“Similar observations have been 3D genome after differentiation in Drosophila Genome Research 621 www.genome.org reported in human cells (Bonev et al. 2017; Freire-Pritchett et al. 2017),whichsuggeststhatthereorganizationduringdevelopment is conserved during evolution.”
Three-dimensional organization and dynamics of the genome
Szałaj, P., & Plewczyński, D. (2018) · Cell Biology and Toxicology · doi:10.1007/s10565-018-9428-y · Cited by 54 · see citing works
Integrative single-cell RNA-seq and ATAC-seq analysis of myogenic differentiation in pig
Cai, S., Hu, B., Wang, X., Liu, T., Lin, Z., Tong, X., Xu, R., Chen, M., Duo, T., Zhu, Q., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01519-z · Cited by 55 · see citing works
“The cis-regulatory contact upon lineage commitment is a dynamic process that includes acquiring and losing specific promoter interactions [61].”
BackgroundRegulation of Chromatin Structure During Neural Development
Kishi, Y., & Gotoh, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00874 · Cited by 50 · see citing works
Chovanec, P., Collier, A. J., Krueger, C., Várnai, C., Semprich, C. I., Schoenfelder, S., Corcoran, A. E., & Rugg‐Gunn, P. J. (2021) · Nature Communications · doi:10.1038/s41467-021-22201-4 · Cited by 48 · see citing works
Self-citationRaviram, R., Rocha, P. P., Luo, V. M., Swanzey, E., Miraldi, E. R., Chuong, E. B., Feschotte, C., Bonneau, R., & Skok, J. A. (2018) · Genome biology · doi:10.1186/s13059-018-1598-7 · Cited by 51 · see citing works
Thompson, J. J., Lee, D. J., Mitra, A., Frail, S., Dale, R., & Rocha, P. P. (2022) · Nature Communications · doi:10.1038/s41467-022-31938-5 · Cited by 47 · see citing works
Enhancers in the Peril lincRNA locus regulate distant but not local genes
Groff, A. F., Barutcu, A. R., Lewandowski, J. P., & Rinn, J. L. (2018) · Genome biology · doi:10.1186/s13059-018-1589-8 · Cited by 41 · see citing works
Pahl, M. C., Doege, C. A., Hodge, K. M., Littleton, S. H., Leonard, M. E., Lu, S., Rausch, R., Pippin, J. A., Rosa, M. C. D., Basak, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27001-4 · Cited by 46 · see citing works
Koohy, H., Bolland, D. J., Matheson, L. S., Schoenfelder, S., Stellato, C., Dimond, A., Várnai, C., Chovanec, P., Chessa, T. A. M., Denizot, J., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1489-y · Cited by 38 · see citing works
“7e), in contrast to findings in other systems such as ES cell differentiation [34].”
ResultSelf-citationSu, C., Argenziano, M., Lu, S., Pippin, J. A., Pahl, M. C., Leonard, M. E., Cousminer, D. L., Johnson, M. E., Lasconi, C., Wells, A. D., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102000 · Cited by 40 · see citing works
Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
Clément, Y., Torbey, P., Gilardi‐Hebenstreit, P., & Crollius, H. R. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1199 · Cited by 41 · see citing works
Comoglio, F., Park, H. J., Schoenfelder, S., Barozzi, I., Bode, D., Fraser, P., & Green, A. R. (2018) · Genome Research · doi:10.1101/gr.227272.117 · Cited by 41 · see citing works
Self-citationCollier, A. J., & Rugg‐Gunn, P. J. (2018) · BioEssays · doi:10.1002/bies.201700239 · Cited by 40 · see citing works
Self-citationAnalysis of the structural variability of topologically associated domains as revealed by Hi-C
Sauerwald, N., Singhal, A., & Kingsford, C. (2019) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqz008 · Cited by 40 · see citing works
“hESC (H9) Human embryonic stem cell 1 HindIII Dilution GSM2309023 (41) Adrenal gland Tissue 1 HindIII Dilution SRX2179246 (31) Bladder Tissue 2 HindIII Dilution SRX2179247, SRX2179248 (31) DPC Dorsolateral prefrontal cortex tissue 1 HindIII Dilution SRX2179249 (31)”
Balasubramanian, D., Pinto, P. B., Grasso, A., Vincent, S., Tarayre, H., Lajoignie, D., & Ghavi-Helm, Y. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1183 · Cited by 37 · see citing works
“…nature of these interactions and the elements involved have not been studied in detail, promoter-interacting regions were found to be enriched in histone marks associated with active enhancers, active promoters, and transcribed regions, highly suggestive of non-coding regulatory elements ( 29 ).”
BackgroundInfluentialYun, H.-Y., Narayan, N., Vohra, S., Giotopoulos, G., Mupo, A., Madrigal, P., Sasca, D., Lara-Astiaso, D., Horton, S., Agrawal-Singh, S., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00925-9 · Cited by 14 · see citing works
“…11% of all high-confidence interactions were significantly differential (gained or lost) in SM or DM HSPC, based on stringent alterations of the ranking of CHiCAGO scores 29,30 (Figure 4g), with more interactions lost than newly formed in the mutant states (Figure 4h and Supplementary Table 8).”
Self-citationDetecting chromosomal interactions in Capture Hi-C data with CHiCAGO and companion tools
Freire-Pritchett, P., Ray-Jones, H., Rosa, M. D., Eijsbouts, C., Orchard, W. R., Wingett, S., Wallace, C., Cairns, J. M., Spivakov, M., & Malysheva, V. (2021) · Nature Protocols · doi:10.1038/s41596-021-00567-5 · Cited by 34 · see citing works
Self-citationChromatin modules and their implication in genomic organization and gene regulation
van Mierlo, G., Pushkarev, O., Kribelbauer, J. F., & Deplancke, B. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.11.003 · Cited by 32 · see citing works
Navigating the non-coding genome in heart development and Congenital Heart Disease
Chahal, G., Tyagi, S., & Ramialison, M. (2019) · Differentiation · doi:10.1016/j.diff.2019.05.001 · Cited by 35 · see citing works
Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Schoenfelder, S., Javierre, B. M., Furlan-Magaril, M., Wingett, S., & Fraser, P. (2018) · Journal of Visualized Experiments · doi:10.3791/57320-v · Cited by 34 · see citing works
Self-citationLaverré, A., Tannier, É., & Necşulea, A. (2021) · Genome Research · doi:10.1101/gr.275901.121 · Cited by 30 · see citing works
A complex regulatory landscape involved in the development of mammalian external genitals
Amândio, A. R., Lopez‐Delisle, L., Bolt, C. C., Mascrez, B., & Duboule, D. (2020) · eLife · doi:10.7554/elife.52962 · Cited by 26 · see citing works
Wolfe, J. C., Mikheeva, L. A., Hagras, H., & Zabet, N. R. (2021) · Genome biology · doi:10.1186/s13059-021-02532-7 · Cited by 27 · see citing works
“To achieve regulation of distal target genes, enhancers must make 3D contacts with the promoters of genes that they control [9].”
3D genome organization links non-coding disease-associated variants to genes
Orozco, G., Schoenfelder, S., Walker, N. J., Eyre, S., & Fraser, P. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.995388 · Cited by 27 · see citing works
“Furthermore, although cell differentiation is often characterized by dynamic rewiring of promoter-enhancer loops (Freire-Pritchett et al., 2017; Siersbæk et al., 2017), some specific interactions do not contemporaneously drive gene expression.”
BackgroundSelf-citationBlank spots on the map: some current questions on nuclear organization and genome architecture
Adriaens, C., Serebryannyy, L., Feric, M., Schibler, A., Meaburn, K. J., Kubben, N., Trzaskoma, P., Shachar, S., Vidak, S., Finn, E. H., et al. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1726-1 · Cited by 26 · see citing works
Middelkamp, S., Vlaar, J. M., Giltay, J. C., Korzelius, J., Besselink, N. J. M., Boymans, S., Janssen, R., de la Fonteijne, L., van Binsbergen, E., van Roosmalen, M. J., et al. (2019) · Genome Medicine · doi:10.1186/s13073-019-0692-0 · Cited by 26 · see citing works
“The bottom track displays the PCHiC 795 interactions of the HOXD13 gene in neuroectodermal cells [42].”
BackgroundContributions of 3D chromatin structure to cell-type-specific gene regulation
Schaeffer, M., & Nöllmann, M. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102032 · Cited by 26 · see citing works
FoxA1/2-dependent epigenomic reprogramming drives lineage switching in lung adenocarcinoma
Gillis, K., Orellana, W. A., Wilson, E., Parnell, T. J., Fort, G., Fang, P., Dadzie, H. E., Murphy, B., Zhang, X., & Snyder, E. L. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.10.009 · Cited by 23 · see citing works
Su, C., Pahl, M. C., Grant, S. F. A., & Wells, A. D. (2021) · Human Genetics · doi:10.1007/s00439-021-02326-8 · Cited by 24 · see citing works
Decoding the organization, dynamics, and function of the 4D genome
Aboelnour, E., & Bonev, B. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.023 · Cited by 21 · see citing works
Vijayabaskar, M. S., Goode, D. K., Obier, N., Lichtinger, M., Emmett, A., Abidin, F. N. Z., Shar, N. A., Hannah, R., Assi, S. A., Lie‐A‐Ling, M., et al. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007337 · Cited by 19 · see citing works
“This coCRE comprises of the promoter and a -17kB upstream region, which has been shown to be involved in Spi1 expression control [28].”
BackgroundWelzenbach, J., Hammond, N. L., Nikolić, M., Thieme, F., Ishorst, N., Leslie, E. J., Weinberg, S. M., Beaty, T. H., Marazita, M. L., Mangold, E., et al. (2021) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2021.100038 · Cited by 21 · see citing works
“, DNA-DNA interactions of enhancers and TSS) at specific risk loci, we accessed pCHi-C cis-interaction data collected in hESCs (GEO: GSE86821).(41)”
MethodVisualizing Structure and Transitions for Biological Data ExplorationPreprint
Moon, K. R., van Dijk, D., Wang, Z., Burkhardt, D. B., Chen, W. S., Yim, K., van den Elzen, A. M. G., Hirn, M., Coifman, R. R., Ivanova, N. B., et al. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3155891 · Cited by 22 · see citing works
“To show that the PHATE embedding agrees with known biology, we compared the scRNA-seq data with bulk RNA-seq data available from the literature including datasets from ESCs [64]; ESC-derived neuroectodermal cells (NEC) [65]; ESC differentiating into neural progenitor cells (NPC) at days 0, 8, and 16 [66]; neural crest…”
MethodApplication of Hi-C and other omics data analysis in human cancer and cell differentiation research
Gong, H., Yang, Y., Zhang, S., Li, M.-H., & Zhang, X.-T. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.04.016 · Cited by 17 · see citing works
Rosa, M. D., & Spivakov, M. (2020) · Nature Genetics · doi:10.1038/s41588-020-0583-8 · Cited by 19 · see citing works
Self-citationSignaling‐to‐chromatin pathways in the immune system
de Paz, A. M., & Josefowicz, S. Z. (2021) · Immunological Reviews · doi:10.1111/imr.12955 · Cited by 18 · see citing works
preciseTAD: a transfer learning framework for 3D domain boundary prediction at base-pair resolution
Stilianoudakis, S. C., Marshall, M. A., & Dozmorov, M. G. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab743 · Cited by 18 · see citing works
Enhancer-Promoter Communication: It’s Not Just About Contact
Wurmser, A., & Basu, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.867303 · Cited by 17 · see citing works
Huang, H., Liu, J., Li, M., Guo, H., Zhu, J., Zhu, L., Wu, S., Mo, K., Huang, Y., Tan, J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo5668 · Cited by 17 · see citing works
“These chromatin interactions identified promoter interaction regions with active enhancer that are enriched for epigenomic features, such as H3K4me1 and H3K27ac, which was consistent with the results of several recent elegant studies, demonstrating that forced looping of enhancers to promoters induces gene activation…”
ResultGenetic coupling of enhancer activity and connectivity in gene expression control
Ray-Jones, H. F., Sung, C. K., Chan, L. T., Haglund, A., Artemov, P., Rosa, M. D., Ruje, L., Burden, F., Kreuzhuber, R., Litovskikh, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-55900-3 · Cited by 17 · see citing works
Self-citationInterplay between regulatory elements and chromatin topology in cellular lineage determination.
Shukla, V., Cetnarowska, A., Hyldahl, M., & Mandrup, S. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.05.011 · Cited by 9 · see citing works
Feldmann, A., Dimitrova, E., Kenney, A., Lastuvkova, A., & Klose, R. J. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa064 · Cited by 15 · see citing works
“Firstly, they are not maintained upon differentiation-induced gene activation as is the case for other stimuli-induced interactions (46), developmental genes (25), or interactions described in other developmental model systems (2,45).”
BackgroundArrastia, M. V., Jachowicz, J. W., Ollikainen, N., Curtis, M. S., Lai, C., Quinodoz, S. A., Selck, D. A., Guttman, M., & Ismagilov, R. F. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.11.242081 · Cited by 15 · see citing works
González-Ramírez, M., Ballaré, C., Mugianesi, F., Beringer, M., Santanach, A., Blanco, E., & Croce, L. D. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1009368 · Cited by 14 · see citing works
Molecular Basis of the Function of Transcriptional Enhancers
Ibragimov, A. N., Bylino, O. V., & Shidlovskii, Y. V. (2020) · Cells · doi:10.3390/cells9071620 · Cited by 14 · see citing works
Wei, X., Xu, Y.-Y., Yang, D.-C., Kim, K., Yi, L., Luo, W.-Z., Lin, X., Xiang, Y., Williams, A. B., Wang, X.-T., et al. (2026) · Nature Biotechnology · doi:10.1038/s41587-026-03013-7 · Cited by 16 · see citing works
Salviato, E., Djordjilović, V., Hariprakash, J. M., Tagliaferri, I., Pal, K., & Ferrari, F. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab547 · Cited by 13 · see citing works
Making connections: enhancers in cellular differentiation
Herrmann, J. C., Beagrie, R. A., & Hughes, J. R. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.10.008 · Cited by 13 · see citing works
Pavlaki, I., Shapiro, M., Pisignano, G., Jones, S. M. E., Telenius, J. M., Descalzo, S. M., Williams, R. J., Hughes, J. R., & Vance, K. W. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1010230 · Cited by 13 · see citing works
The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation
Golkaram, M., Jang, J., Hellander, S., Kosik, K. S., & Petzold, L. R. (2017) · Scientific Reports · doi:10.1038/s41598-017-13731-3 · Cited by 14 · see citing works
Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networks
Todd, C. D., Ijaz, J., Torabi, F., Dovgusha, O., Bevan, S., Cracknell, O., Lohoff, T., Clark, S. J., Argelaguet, R., Pearce, J., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03658-8 · Cited by 12 · see citing works
“…tissues we are investigating, we utilised a combination of genomic proximity models and Promoter Capture Hi-C data of mEpiLCs/hESCs [21, 24] to assign enhancers to promoters they likely interact with, as previous studies have shown that enhancers can interact with promoters prior to…”
Self-citationEpigenome rewiring in human pluripotent stem cells
Yan, J., & Huangfu, D. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.001 · Cited by 9 · see citing works
Fernández-Valverde, S. L., Aguilera, F., & Ramos-Díaz, R. A. (2018) · Integrative and Comparative Biology · doi:10.1093/icb/icy061 · Cited by 12 · see citing works
Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation
Alavattam, K. G., Mitzelfelt, K. A., Bonora, G., Fields, P., Yang, X., Chiu, H. S., Pabon, L., Bertero, A., Palpant, N. J., Noble, W. S., et al. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.11.003 · Cited by 10 · see citing works
“While work remains to understand how TADs strengthen and PPIs arise in endothelial cells, our findings indicate that these features are influenced by stable and dynamic compartments to regulate transcription necessary for differentiation: strengthened TAD boundaries are accompanied by increased numbers of intra-TAD co…”
Multi-layered transcriptional control of cranial neural crest development
Candido-Ferreira, I., Lukoseviciute, M., & Sauka‐Spengler, T. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.07.010 · Cited by 8 · see citing works
Comoglio, F., Park, H. J., Schoenfelder, S., Barozzi, I., Bode, D., Fraser, P., & Green, A. R. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/163113 · Cited by 9 · see citing works
Self-citationGolov, A. K., Gavrilov, A. A., Kaplan, N., & Razin, S. V. (2024) · eLife · doi:10.7554/elife.91596.3 · Cited by 8 · see citing works
Rinzema, N. J., Sofiadis, K., Tjalsma, S. J. D., Verstegen, M. J. A. M., Oz, Y., Valdes-Quezada, C., Felder, A.-K., Filipovska, T., van der Elst, S., de Andrade dos Ramos, Z., et al. (2021) · doi:10.1101/2021.10.05.463209 · Cited by 8 · see citing works
Transient promoter interactions modulate developmental gene activation
Mahara, S., Prüssing, S., Smialkovska, V., Krall, S., Holliman, S., Blum, B., Dachtler, V., Borgers, H., Sollier, E., Plass, C., et al. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.10.005 · Cited by 8 · see citing works
Zibetti, C. (2022) · Cells · doi:10.3390/cells11050806 · Cited by 6 · see citing works
Regulatory de novo mutations underlying intellectual disability
Vas, M. G. D., Boulet, F., Joshi, S. S., Garstang, M. G., Khan, T. N., Atla, G., Parry, D., Moore, D., Cebola, I., Zhang, S., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201843 · Cited by 6 · see citing works
“The significant interactions between promoters and enhancers identified using PCHi-C in neuronal progenitor cells (21) were used to assign target genes to the DNM-containing enhancers.”
Cellular reprogramming is driven by widespread rewiring of promoter-enhancer interactions
Wang, M., He, B., Hao, Y., Srinivasan, D., Shrinet, J., & Fraser, P. (2023) · BMC Biology · doi:10.1186/s12915-023-01766-0 · Cited by 5 · see citing works
“PCHi-C studies have shown dynamic rewiring of enhancer-promoter interactions during human ESC differentiation to neuroectodermal cells [22], during mouse adipocyte differentiation [7], and during keratinogenesis [23] suggesting that promoter interaction changes regulate gene expression associated…”
BackgroundSelf-citationAlgorithmic considerations when analysing capture Hi-C data
Disney–Hogg, L., Kinnersley, B., & Houlston, R. S. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.16394.1 · Cited by 6 · see citing works
Malysheva, V., Mendoza-Parra, M. A., Blum, M., Spivakov, M., & Gronemeyer, H. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/303842 · Cited by 6 · see citing works
Self-citationGolov, A. K., Gavrilov, A. A., Kaplan, N., & Razin, S. V. (2023) · eLife · doi:10.7554/elife.91596 · Cited by 5 · see citing works
- Authors
- Freire-Pritchett, P., Schoenfelder, S., Várnai, C., Wingett, S. W., Cairns, J., Collier, A. J., García-Vílchez, R., Furlan-Magaril, M., Osborne, C. S., Fraser, P., Rugg-Gunn, P. J., & Spivakov, M.
- Affiliations
- Babraham Institute (GB)
- King's College London (GB)
- Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom
- Corresponding author
- Spivakov, Mikhail
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-03-23
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5407860
- OpenAlex
- W2602710346
- Cited by
- 161
- References
- 88
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 20 · 2021: 25 · 2020: 17 · 2019: 19 · 2018: 24 · 2017: 6
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- Wellcome (WT093736)
- Biotechnology and Biological Sciences Research Council (BB/J004480/1)
- Medical Research Council (MR/J003808/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- cis-regulatory elements, enhancers, lineage commitment, human embryonic stem cells, chromatin interactions, promoter capture Hi-C, enhancer target genes, pluripotency
- MeSH terms
- Human Embryonic Stem Cells, Cell Differentiation, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Transcription, Genetic, Regulatory Elements, Transcriptional
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
