The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
A unique chromatin signature uncovers early developmental enhancers in humans
Open accessAbstract
Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The TRIM33-occupied regions upstream of Bim and Atp1b3 were enriched for H3K27 acetylation but not for H3K4 tri-methylation, suggesting that these elements are active enhancers”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Rada-Iglesias et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Since H3K27ac modification reliably marks active enhancers located in the distal regions of a given gene, 34”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [34]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Currently mono-methylation of histone H3 lysine 4 (H3K4me1), associated with the binding of Trithorax/MLL complexes, is taken to be the hallmark of both ‘primed’ and active enhancers, whilst active enhancers additionally tend to associate with the acetylation of histone H3 lysine 27 (H3K27ac) [133–137].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [135]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Previous studies suggested that higher levels and a bimodal distribution pattern of monomethylated histone 3 lysine 4 (H3K4me1) correlate with enhancer function (Hoffman et al., 2010; Rada-Iglesias et al., 2011).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Rada-Iglesias et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“In addition to the ‘primed’ and active states, enhancers can also reside in a ‘poised’ state exhibiting both H3K4me1 and H3 lysine 27 trimethylation (H3K27me3) that is associated with Polycomb repressive complexes [131, 135, 136, 138].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [135]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We inhibited p300 catalytic activity with the small molecule A48530, but did not observe a decrease in TF binding (Fig. 2N–O vs. Fig. 2B–C) or nucleosome occupancy (Fig. S3M), despite a marked reduction in H3K27 acetylation (Fig. S3N)”
From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [30]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.020 · Cited by 4,505
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
Heintzman, 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
Histone 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
Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors
Ieda, M., Fu, J.-D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G., & Srivastava, D. (2010) · Cell · doi:10.1016/j.cell.2010.07.002 · Cited by 2,454
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells
Guenther, M. G., Levine, S. S., Boyer, L. A., Jaenisch, R., & Young, R. A. (2007) · Cell · doi:10.1016/j.cell.2007.05.042 · Cited by 2,002
ChIP-seq accurately predicts tissue-specific activity of enhancers
Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., et al. (2009) · Nature · doi:10.1038/nature07730 · Cited by 1,639
c-Myc Regulates Transcriptional Pause Release
Rahl, P. B., Lin, C. Y., Seila, A. C., Flynn, R. A., McCuine, S., Burge, C. B., Sharp, P. A., & Young, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.03.030 · Cited by 1,279
Self-citationVISTA 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
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–400 of 1,013
Chromatin accessibility dynamics reveal novel functional enhancers in C. elegansPreprint
Daugherty, A. C., Yeo, R. W., Buenrostro, J. D., Greenleaf, W. J., Kundaje, A. B., & Brunet, A. (2017) · Genome Research · doi:10.1101/gr.226233.117 · Cited by 177
In search of the determinants of enhancer–promoter interaction specificity
van Arensbergen, J., van Steensel, B., & Bussemaker, H. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.004 · Cited by 180
Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation
Tsagaratou, A., Äijö, T., Lio, C. J., Yue, X., Huang, Y., Jacobsen, S. E., Lähdesmäki, H. J., & Rao, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412327111 · Cited by 186
Polycomb-Repressed Genes Have Permissive Enhancers that Initiate Reprogramming
Taberlay, P. C., Kelly, T. K., Liu, C.-C., You, J. S., De Carvalho, D. D., Miranda, T. B., Zhou, X. J., Liang, G., & Jones, P. A. (2011) · Cell · doi:10.1016/j.cell.2011.10.040 · Cited by 171
Werner, M. S., & Ruthenburg, A. J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.033 · Cited by 180
Transcription and enhancer profiling in human monocyte subsets
Schmidl, C., Renner, K., Peter, K., Eder, R., Lassmann, T., Balwierz, P. J., Itoh, M., Nagao-Sato, S., Kawaji, H., Carninci, P., et al. (2014) · Blood · doi:10.1182/blood-2013-02-484188 · Cited by 178
ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
Cato, L., de Tribolet-Hardy, J., Lee, I. I., Rottenberg, J. T., Coleman, I. M., Melchers, D., Houtman, R., Xiao, T., Li, W., Uo, T., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.008 · Cited by 171
Li, L., Bowling, S., McGeary, S. E., Yu, Q., Lemke, B., Alcedo, K., Jia, Y., Liu, X., Ferreira, M., Klein, A. M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.09.019 · Cited by 167
Roles of H3K4 methylation in biology and disease
Wang, H., & Helin, K. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.06.001 · Cited by 177
Epigenetics of hematopoiesis and hematological malignanciesPreprint
Hu, D., & Shilatifard, A. (2016) · Genes & Development · doi:10.1101/gad.284109.116 · Cited by 175
Insights into the genetic architecture of the human face
White, J. D., Indencleef, K., Naqvi, S., Eller, R. J., Hoskens, H., Roosenboom, J., Lee, M. K., Li, J., Mohammed, J., Richmond, S., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00741-7 · Cited by 166
Self-citationSetting appropriate boundaries: Fate, patterning and competence at the neural plate border
Groves, A. K., & LaBonne, C. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.11.027 · Cited by 166
Peterson, K. A., Nishi, Y., Ma, W., Vedenko, A., Shokri, L., Zhang, X., McFarlane, M., Baizabal, J., Junker, J. P., van Oudenaarden, A., et al. (2012) · Genes & Development · doi:10.1101/gad.207142.112 · Cited by 166
Enhancer Malfunction in Cancer
Herz, H., Hu, D., & Shilatifard, A. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.033 · Cited by 170
Regulation of histone H3K4 methylation in brain development and disease
Shen, E., Shulha, H. P., Weng, Z., & Akbarian, S. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0514 · Cited by 167
FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis
Webb, A. E., Pollina, E. A., Vierbuchen, T., Urbán, N., Ucar, D., Leeman, D. S., Martynoga, B., Sewak, M., Rando, T. A., Guillemot, F., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.035 · Cited by 164
Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence
Sen, P., Lan, Y., Li, C. Y., Sidoli, S., Donahue, G., Dou, Z., Frederick, B., Chen, Q., Luense, L. J., Garcia, B. A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.021 · Cited by 164
MLL3/MLL4/COMPASS Family on Epigenetic Regulation of Enhancer Function and Cancer
Sze, C. C., & Shilatifard, A. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026427 · Cited by 164
Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages
Obaldia, M. E. D., & Bhandoola, A. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112032 · Cited by 167
Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure
Greco, C. M., & Condorelli, G. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.71 · Cited by 162
Positively selected enhancer elements endow osteosarcoma cells with metastatic competence
Morrow, J. J., Bayles, I., Funnell, A. P. W., Miller, T. E., Saiakhova, A., Lizardo, M. M., Bartels, C. F., Kapteijn, M. Y., Hung, S., Mendoza, A., et al. (2018) · Nature Medicine · doi:10.1038/nm.4475 · Cited by 161
Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
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., et al. (2017) · eLife · doi:10.7554/elife.21926 · Cited by 161
“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).”
BackgroundChicas, A., Kapoor, A., Wang, X., Aksoy, O., Evertts, A. G., Zhang, M. Q., Garcia, B. A., Bernstein, E., & Lowe, S. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119836109 · Cited by 162
Pioneer factors: directing transcriptional regulators within the chromatin environment
Magnani, L., Eeckhoute, J., & Lupien, M. (2011) · Trends in Genetics · doi:10.1016/j.tig.2011.07.002 · Cited by 173
Drp1-mediated mitochondrial fission promotes renal fibroblast activation and fibrogenesis
Wang, Y., Lu, M., Xiong, L., Fan, J., Zhou, Y., Li, H., Peng, X., Zhong, Z., Wang, Y., Huang, F., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-019-2218-5 · Cited by 161
Leslie, E. J., Taub, M. A., Liu, H., Steinberg, K. M., Koboldt, D. C., Zhang, Q., Carlson, J. C., Hetmanski, J. B., Wang, H., Larson, D. E., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.01.004 · Cited by 161
Wang, X., He, L., Goggin, S. M., Saadat, A., Wang, L., Sinnott-Armstrong, N., Claussnitzer, M., & Kellis, M. (2018) · Nature Communications · doi:10.1038/s41467-018-07746-1 · Cited by 159
Factor, D. C., Corradin, O., Zentner, G. E., Saiakhova, A., Song, L., Chenoweth, J. G., McKay, R. D. G., Crawford, G. E., Scacheri, P. C., & Tesar, P. J. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.05.005 · Cited by 159
Berthelot, C., Villar, D., Horvath, J. E., Odom, D. T., & Flicek, P. (2017) · Nature Ecology & Evolution · doi:10.1038/s41559-017-0377-2 · Cited by 163
lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation
Daneshvar, K., Ardehali, M. B., Klein, I. A., Hsieh, F., Kratkiewicz, A. J., Mahpour, A., Cancelliere, S., Zhou, C., Cook, B. M., Li, W., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0572-2 · Cited by 164
Schödel, J., Bardella, C., Sciesielski, L. K., Brown, J. M., Pugh, C. W., Buckle, V. J., Tomlinson, I. P. M., Ratcliffe, P. J., & Mole, D. R. (2012) · Nature Genetics · doi:10.1038/ng.2204 · Cited by 163
Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription
Cerbo, V. D., Mohn, F., Ryan, D., Montellier, E., Kacem, S., Tropberger, P., Kallis, E., Holzner, M., Hoerner, L., Feldmann, A., et al. (2014) · eLife · doi:10.7554/elife.01632 · Cited by 171
Lu, R., Wang, P., Parton, T., Zhou, Y., Chrysovergis, K., Rockowitz, S., Chen, W., Abdel-Wahab, O. I., Wade, P. A., Zheng, D., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.008 · Cited by 162
Kaaij, L. J. T., Mohn, F., van der Weide, R. H., de Wit, E., & Bühler, M. (2019) · Cell · doi:10.1016/j.cell.2019.08.007 · Cited by 161
Integrating Diverse Datasets Improves Developmental Enhancer Prediction
Erwin, G. D., Oksenberg, N., Truty, R., Kostka, D., Murphy, K. K., Ahituv, N., Pollard, K. S., & Capra, J. A. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003677 · Cited by 156
Molecular features of cellular reprogramming and development
Smith, Z. D., Sindhu, C., & Meissner, A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.6 · Cited by 155
Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancersPreprint
Loft, A., Forss, I., Siersbæk, M. S., Schmidt, S. F., Larsen, A.-S. B., Madsen, J. G. S., Pisani, D. F., Nielsen, R., Aagaard, M. M., Mathison, A., et al. (2014) · Genes & Development · doi:10.1101/gad.250829.114 · Cited by 159
Genomic Perspectives of Transcriptional Regulation in Forebrain Development
Nord, A. S., Pattabiraman, K., Visel, A., & Rubenstein, J. L. R. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.011 · Cited by 152
BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis
Richart, L., Pau, E. C. D. S., Rio‐Machín, A., de Andrés, M. P., Cigudosa, J. C., Lobo, V. J. S.-A., & Real, F. X. (2016) · Nature Communications · doi:10.1038/ncomms10153 · Cited by 155
Kraushaar, D. C., Jin, W., Maunakea, A. K., Abraham, B. J., Ha, M., & Zhao, K. (2013) · Genome biology · doi:10.1186/gb-2013-14-10-r121 · Cited by 151
Evolution of Alu Elements toward Enhancers
Su, M., Han, D., Boyd-Kirkup, J. D., Yu, X., & Han, J.-D. J. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.011 · Cited by 157
Predicting enhancer transcription and activity from chromatin modifications
Zhu, Y. K., Sun, L., Zhao, C., Whitaker, J. W., Wang, T., & Wang, W. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt826 · Cited by 157
Genome organization and long-range regulation of gene expression by enhancers
Smallwood, A., & Ren, B. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.02.005 · Cited by 155
Transcription shapes genome-wide histone acetylation patterns
Martin, B. J. E., Brind’Amour, J., Kuzmin, A., Jensen, K. N., Liu, Z. C., Lorincz, M. C., & Howe, L. J. (2021) · Nature Communications · doi:10.1038/s41467-020-20543-z · Cited by 160
TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma
Lv, D., Li, Y., Zhang, W., Alvarez, A. A., Song, L., Tang, J., Gao, W., Hu, B., Cheng, S., & Feng, H. (2017) · Nature Communications · doi:10.1038/s41467-017-01731-w · Cited by 150
Karr, J. P., Ferrie, J. J., Tjian, R., & Darzacq, X. (2021) · Genes & Development · doi:10.1101/gad.349160.121 · Cited by 155
Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag
Bartosovic, M., & Castelo-Branco, G. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01535-4 · Cited by 146
Gaarenstroom, T., & Hill, C. S. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.01.009 · Cited by 151
DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation
Godfrey, L., Crump, N. T., Thorne, R., Lau, I., Repapi, E., Dimou, D., Smith, A., Harman, J. R., Telenius, J. M., Oudelaar, A. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10844-3 · Cited by 154
Transcriptional Control of Circadian Rhythms and Metabolism: A Matter of Time and Space
Kim, Y. H., & Lazar, M. A. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa014 · Cited by 154
High-throughput functional comparison of promoter and enhancer activities
Nguyen, T. A., Jones, R. D., Snavely, A. R., Pfenning, A. R., Kirchner, R., Hemberg, M., & Gray, J. M. (2016) · Genome Research · doi:10.1101/gr.204834.116 · Cited by 146
Mechanisms 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 151
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
Enhancers: emerging roles in cell fate specification
Ong, C., & Corces, V. G. (2012) · The EMBO Reports · doi:10.1038/embor.2012.52 · Cited by 144
Gene bivalency at Polycomb domains regulates cranial neural crest positional identity
Minoux, M., Holwerda, S. J. B., Vitobello, A., Kitazawa, T., Kohler, H., Stadler, M. B., & Rijli, F. M. (2017) · Science · doi:10.1126/science.aal2913 · Cited by 148
Lin, J., & Leonard, W. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041447 · Cited by 150
FOXA2 Is Required for Enhancer Priming during Pancreatic Differentiation
Lee, K., Cho, H., Rickert, R. W., Li, Q. V., Pulecio, J., Leslie, C. S., & Huangfu, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.034 · Cited by 144
Placing the HIRA Histone Chaperone Complex in the Chromatin Landscape
Pchelintsev, N. A., McBryan, T., Rai, T. S., van Tuyn, J., Ray-Gallet, D., Almouzni, G., & Adams, P. D. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.026 · Cited by 143
Brown, C. C., Esterházy, D., Sarde, A., London, M., Pullabhatla, V., Osma-García, I. C., al-Bader, R., Ortiz, C., Elgueta, R., Arno, M. J., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.003 · Cited by 147
Diaferia, G. R., Balestrieri, C., Prosperini, E., Nicoli, P., Spaggiari, P., Zerbi, A., & Natoli, G. (2016) · The EMBO Journal · doi:10.15252/embj.201592404 · Cited by 149
Super-enhancer function and its application in cancer targeted therapy
Tang, F., Yang, Z., Tan, Y., & Li, Y. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0108-z · Cited by 145
Reactivation of the pluripotency program precedes formation of the cranial neural crest
Zalc, A., Sinha, R., Gulati, G. S., Wesche, D. J., Daszczuk, P., Swigut, T., Weissman, I. L., & Wysocka, J. (2021) · Science · doi:10.1126/science.abb4776 · Cited by 153
Self-citationLarge-Scale Quality Analysis of Published ChIP-seq Data
Marinov, G. K., Kundaje, A. B., Park, P. J., & Wold, B. J. (2013) · G3 Genes Genomes Genetics · doi:10.1534/g3.113.008680 · Cited by 146
Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development
Ngan, C. Y., Wong, C. H., Tjong, H., Wang, W., Goldfeder, R. L., Choi, C., He, H., Gong, L., Lin, J., Urban, B., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0581-x · Cited by 140
Genome-wide mapping of autonomous promoter activity in human cells
van Arensbergen, J., FitzPatrick, V. D., de Haas, M., Pagie, L., Sluimer, J., Bussemaker, H. J., & van Steensel, B. (2017) · Nature Biotechnology · doi:10.1038/nbt.3754 · Cited by 140
Nucleosome-Driven Transcription Factor Binding and Gene Regulation
Ballaré, C., Castellano, G., Gaveglia, L., Althammer, S., González‐Vallinas, J., Eyras, E., Dily, F. L., Zaurín, R., Soronellas, D., Vicent, G. P., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.10.019 · Cited by 147
Kidder, B. L., Hu, G., & Zhao, K. (2014) · Genome biology · doi:10.1186/gb-2014-15-2-r32 · Cited by 142
Plant Enhancers: A Call for Discovery
Weber, B., Zicola, J., Oka, R., & Stam, M. E. (2016) · Trends in Plant Science · doi:10.1016/j.tplants.2016.07.013 · Cited by 144
Grassi, L., Pourfarzad, F., Ullrich, S., Merkel, A., Were, F., Pau, E. C. D. S., Yi, G., Hiemstra, I. H., Tool, A. T. J., Mul, E. P. J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.018 · Cited by 142
Huang, Z., Du, G., Huang, X., Li, H., Han, X., Xu, B., Zhang, Y., Yu, M., Qin, Y., Xia, Y., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.015 · Cited by 142
H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cellsPreprint
Fernandez-Fernandez, A., Bayón, G. F., Urdinguio, R. G., Toraño, E. G., García, M. G., Carella, A., Petrus-Reurer, S., Ferrero, C., Martinez-Camblor, P., Cubillo, I., et al. (2014) · Genome Research · doi:10.1101/gr.169011.113 · Cited by 140
Ryu, A. H., Eckalbar, W. L., Kreimer, A., Yosef, N., & Ahituv, N. (2017) · Scientific Reports · doi:10.1038/s41598-017-07757-w · Cited by 139
Transcriptional enhancers in development and disease
Sakabe, N. J., Savic, D., & Nóbrega, M. A. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-238 · Cited by 143
Lee, B.-K., Bhinge, A., Battenhouse, A., McDaniell, R. M., Liu, Z., Song, L., 倪, 运., Birney, E., Lieb, J. D., Furey, T. S., et al. (2011) · Genome Research · doi:10.1101/gr.127597.111 · Cited by 138
Schleicher, U., Paduch, K., Debus, A., Obermeyer, S., König, T., Kling, J. C., Ribechini, E., Dudziak, D., Mougiakakos, D., Murray, P. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.001 · Cited by 136
“This histonemark is highly enriched at active cis-regulatory regions (promoters and enhancers) and directly correlates with chromatin accessibility and transcription of the target gene (Creyghton et al., 2010; Rada-Iglesias et al., 2011).”
Functional assessment of human enhancer activities using whole-genome STARR-sequencing
Liu, Y., Yu, S., Dhiman, V. K., Brunetti, T., Eckart, H., & White, K. P. (2017) · Genome Biology · doi:10.1186/s13059-017-1345-5 · Cited by 136
Xia, C., Tao, Y., Li, M., Che, T., & Qu, J. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9073 · Cited by 136
Park, D. H., Hong, S. J., Salinas, R. D., Liu, S. J., Sun, S. W., Sgualdino, J., Testa, G., Matzuk, M. M., Iwamori, N., & Lim, D. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.060 · Cited by 139
Discovery of active enhancers through bidirectional expression of short transcripts
Melgar, M., Collins, F. S., & Sethupathy, P. (2011) · Genome biology · doi:10.1186/gb-2011-12-11-r113 · Cited by 142
Gene Regulatory Elements, Major Drivers of Human Disease
Chatterjee, S., & Ahituv, N. (2017) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091416-035537 · Cited by 144
Common and low-frequency variants associated with genome-wide recombination rate
Kong, A., Þorleifsson, G., Frigge, M. L., Másson, G., Gudbjartsson, D. F., Villemoes, R., Magnúsdóttir, E., Olafsdottir, S. B., Þorsteinsdóttir, U., & Stefánsson, K. (2013) · Nature Genetics · doi:10.1038/ng.2833 · Cited by 138
Sugathan, A., & Waxman, D. J. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00280-13 · Cited by 140
Li, L., Cui, L., Lin, P., Liu, Z., Bao, S., Ma, X., Nan, H., Zhu, W., Cen, J., Mao, Y., et al. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.01.009 · Cited by 134
The lysine‐specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer
Rampias, T. N., Karagiannis, D., Avgeris, M., Polyzos, A., Kokkalis, A., Kanaki, Z., Kousidou, E., Tzetis, M., Kanavakis, E., STRAVODIMOS, K. G., et al. (2019) · EMBO Reports · doi:10.15252/embr.201846821 · Cited by 139
Long-range enhancers regulating Myc expression are required for normal facial morphogenesis
Uslu, V. V., Petretich, M., Ruf, S., Langenfeld, K., Fonseca, N. A., Marioni, J. C., & Spitz, F. (2014) · Nature Genetics · doi:10.1038/ng.2971 · Cited by 133
Zhang, H., Zhang, N., Liu, Y., Su, P., Liang, Y., Li, Y., Wang, X., Chen, T., Song, X., Sang, Y., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3418 · Cited by 132
Li, C., Virgilio, M. C., Collins, K. L., & Welch, J. D. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01476-y · Cited by 130
Distant Activation of Transcription: Mechanisms of Enhancer Action
Kulaeva, O. I., Nizovtseva, E. V., Polikanov, Y. S., Ulianov, S. V., & Studitsky, V. M. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.01127-12 · Cited by 136
Pascual‐García, P., Debo, B. M., Aleman, J. R., Talamas, J. A., Lan, Y., Nguyen, N., Won, K., & Capelson, M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.020 · Cited by 130
Dai, X., Bai, Y., Zhao, L., Dou, X., Liu, Y., Wang, L., Li, Y., Li, W., Hui, Y., Huang, X., et al. (2017) · Molecular Plant · doi:10.1016/j.molp.2017.09.007 · Cited by 133
Is histone acetylation the most important physiological function for CBP and p300?
Bedford, D. C., & Brindle, P. K. (2012) · Aging · doi:10.18632/aging.100453 · Cited by 136
Early cardiac development: a view from stem cells to embryos
Vliet, P. P. V., Wu, S. M., Zaffran, S., & Pucéat, M. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs270 · Cited by 129
The three-dimensional genome: regulating gene expression during pluripotency and development
Andrey, G., & Mundlos, S. (2017) · Development · doi:10.1242/dev.148304 · Cited by 134
Long-range interactions between proximal and distal regulatory regions in maize
Li, E., Liu, H., Huang, L., Zhang, X., Dong, X., Song, W., Zhao, H., & Lai, J. (2019) · Nature Communications · doi:10.1038/s41467-019-10603-4 · Cited by 134
Charlet, J., Duymich, C. E., Lay, F. D., Mundbjerg, K., Dalsgaard Sørensen, K., Liang, G., & Jones, P. A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.033 · Cited by 128
Chan, H. L., Beckedorff, F., Zhang, Y., García‐Huidobro, J., Jiang, H. L., Colaprico, A., Bilbao, D., Figueroa, M. E., LaCava, J., Shiekhattar, R., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05728-x · Cited by 135
Andersson, R. (2015) · BioEssays · doi:10.1002/bies.201400162 · Cited by 127
Marcon, E., Jain, H., Bhattacharya, A., Guo, H., Phanse, S., Pu, S., Byram, G., Collins, B. C., Dowdell, E., Fenner, M., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3472 · Cited by 128
Prasad, M. S., Sauka‐Spengler, T., & LaBonne, C. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.03.014 · Cited by 133
Loubiere, V., Papadopoulos, G. L., Szabo, Q., Martinez, A.-M., & Cavalli, G. (2020) · Science Advances · doi:10.1126/sciadv.aax4001 · Cited by 126
Metadata
- Authors
- Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Wysocka, Joanna
- Venue
- Nature
- Published
- 2010-12-15
- Volume
- 470
- Issue
- 7333
- Pages
- 279-283
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4445674
- OpenAlex
- W2154746182
- Cited by
- 2,233
- References
- 39
- Citations by year
- 2026: 70 · 2025: 108 · 2024: 118 · 2023: 134 · 2022: 117 · 2021: 154 · 2020: 162 · 2019: 144 · 2018: 151 · 2017: 158 · 2016: 154 · 2015: 181 · 2014: 190 · 2013: 185 · 2012: 140
- FWCI
- 50.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (K99DE019853)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- enhancers, poised enhancers, human embryonic stem cells, chromatin signatures, H3K4me1, H3K27ac, H3K27me3, P300, SMARCA4, nucleosome density, epiblast, neuroectoderm differentiation, gastrulation, mesoderm formation, neurulation
- MeSH terms
- Acetylation, Animals, Cell Differentiation, Cell Line, Chromatin, DNA Helicases, Enhancer Elements, Genetic, Germ Layers, Histones, Humans, Lysine, Mesoderm, Methylation, Nuclear Proteins, RNA, Transcription Factors, Zebrafish, Gene Expression Regulation, Developmental, Epigenesis, Genetic, Embryonic Development, Chromatin Immunoprecipitation, p300-CBP Transcription Factors, Embryonic Stem Cells, Neural Plate, Neurulation, Gastrulation
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
