The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Controlling Long-Range Genomic Interactions at a Native Locus by Targeted Tethering of a Looping Factor
Open accessAbstract
Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In erythroid cells, the locus control region (LCR) and β-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We employed artificial zinc fingers (ZF) to tether Ldb1 to the β-globin promoter in GATA1 null erythroblasts, in which the β-globin locus is relaxed and inactive. Remarkably, targeting Ldb1 or only its self-association domain to the β-globin promoter substantially activated β-globin transcription in the absence of GATA1. Promoter-tethered Ldb1 interacted with endogenous Ldb1 complexes at the LCR to form a chromatin loop, causing recruitment and phosphorylation of RNA polymerase II. ZF-Ldb1 proteins were inactive at alleles lacking the LCR, demonstrating that their activities depend on long-range interactions. Our findings establish Ldb1 as a critical effector of GATA1-mediated loop formation and indicate that chromatin looping causally underlies gene regulation.
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
“In contrast to YY1 and ZNF143, LDB1 has been shown to form loops independently of both cohesin and CTCF [371, 375].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [371]
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
“LDB1 was first identified as a looping factor in the mouse β-globin locus [317, 371].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [371]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The functional significance of the physical approximation of the promoter to the enhancer was demonstrated in experiments on the activation of transcription through the forced formation of enhancer-promoter loops [87,88].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [88]
The cited source says what the claim attributes to it.
In the citing paper
“Stimulation of promoter activity by forced looping with an enhancer is a strong argument in favor of this model [87,88,110,111].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [88]
In the citing paper
“and physical contact between enhancer-promoter pairs appears to be sufficient for gene activation.26”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [26]
In the citing paper
“Tethering the SA domain to the LCR (L-SA in Figure 1) or β-major promoter (Deng et al., 2012, and data not shown) did not activate βh1-globin expression”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“In adult type murine erythroid cells, Ldb1 is required for the juxtaposition between the LCR and the adult β-major globin gene (Deng et al., 2012; Song et al., 2007).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“These results demonstrated that forced juxtaposition of an enhancer and promoter via chromatin looping can trigger gene activation”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
In the citing paper
“Finally, previous 3C experiments demonstrated the sufficiency of tethered Ldb1 for full reconstitution of an LCR-β-globin promoter loop in immature adult erythroid cells in which the globin locus is otherwise unlooped (Deng et al., 2012).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Deng et al., 2012
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
Capturing Chromosome Conformation
Dekker, J., Rippe, K., Dekker, M., & Kleckner, N. (2002) · Science · doi:10.1126/science.1067799 · Cited by 3,652 · cited 2×
“The use of chromosome conformation capture (3C) and its derivatives has revealed that distant chromosomal elements can be juxtaposed to form chromatin loops, thus providing one mechanism of long-range enhancer function (Cullen et al., 1993; Dekker et al., 2002).”
Looping 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 2×
“…arose from studies of the mammalian b-globin locus, which is among the first gene clusters at which long-range chromosomal interactions between a powerful distal enhancer, the locus control region (LCR), and the target b-globin promoters were described (Carter et al., 2002; Tolhuis et al., 2002).”
Pevny, L., Simon, M. C., Robertson, E., Klein, W. H., Tsai, S.-F., D'Agati, V., Orkin, S. H., & Costantini, F. (1991) · Nature · doi:10.1038/349257a0 · Cited by 1,308 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
Tsai, S., Martin, D. I. K., Zon, L. I., D’Andrea, A. D., Wong, G. G., & Orkin, S. H. (1989) · Nature · doi:10.1038/339446a0 · Cited by 884 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation
Klug, A. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-010909-095056 · Cited by 710 · cited 3×
“ZFs have previously been linked to activation domains to successfully activate gene expression (Klug, 2010).”
InfluentialLong-range chromatin regulatory interactions in vivo
Carter, D., Chakalova, L., Osborne, C. S., Dai, Y.-F., & Fraser, P. (2002) · Nature Genetics · doi:10.1038/ng1051 · Cited by 663 · cited 3×
“Fundamental insights into these issues arose from studies of the mammalian b-globin locus, which is among the first gene clusters at which long-range chromosomal interactions between a powerful distal enhancer, the locus control region (LCR), and the target b-globin promoters were described (Carter et al., 2002; Tolhu…”
Transcriptional regulation of erythropoiesis: an affair involving multiple partners
Cantor, A. B., & Orkin, S. H. (2002) · Oncogene · doi:10.1038/sj.onc.1205326 · Cited by 610 · cited 1×
“However, physical interactions among all of these proteins have been reported (Cantor and Orkin, 2002), making it difficult to distinguish whether they function in linear or parallel pathways.”
The erythroid-specific transcription factor eryf1: A new finger protein
Evans, T., & Felsenfeld, G. (1989) · Cell · doi:10.1016/0092-8674(89)90940-9 · Cited by 580 · cited 1×
“GATA1 is a DNA-binding protein essential for normal erythroid differentiation and b-globin gene expression (Evans and Felsenfeld, 1989; Pevny et al., 1991; Tsai et al., 1989).”
The β-globin nuclear compartment in development and erythroid differentiation
Palstra, R.-J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., & de Laat, W. (2003) · Nature Genetics · doi:10.1038/ng1244 · Cited by 559
Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1
Vakoc, C. R., Letting, D. L., Gheldof, N., Sawado, T., Bender, M. A., Groudine, M., Weiss, M. J., Dekker, J., & Blobel, G. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.028 · Cited by 490 · cited 6×
“Using HS2 as the anchor region, we found that, in parental G1E cells, the 3C signals generally declined with increasing distance (Figure 3A), which is consistent with our previous observations (Vakoc et al., 2005).”
Influential
Flagged first, then by citations
Research works printed but not linked: 1
- Tripic, T., Deng, W., Cheng, Y., Zhang, Y., Vakoc, C.R., Gregory, G.D., Hardison, R.C., and Blobel, G.A. (2009). SCL and associated proteins distinguish active from repressive GATA transcription factor complexes. Blood 113, 2191–2201. · DOI
Cited by
Sorted by citations
Organization and function of the 3D genome
Bonev, B., & Cavalli, G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.112 · Cited by 1,174
Cas9 as a versatile tool for engineering biology
Mali, P., Esvelt, K. M., & Church, G. M. (2013) · Nature Methods · doi:10.1038/nmeth.2649 · Cited by 1,197
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
Exploring 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
“Further, the looping interaction directly stimulates transcription by facilitating recruitment and phosphorylation of RNA polymerase II 39 .”
BackgroundYY1 Is a Structural Regulator of Enhancer-Promoter Loops
Weintraub, A. S., Li, C. H., Zamudio, A. V., Sigova, A. A., Hannett, N. M., Day, D. S., Abraham, B. J., Cohen, M. A., Nabet, B., Buckley, D. L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.11.008 · Cited by 992
“Nonetheless, most recent study of eukaryotic enhancer-promoter interactions has focused on cofactors that lack DNA binding capabilities and bridge enhancer-bound transcription factors and promoter-bound transcription apparatus (Allen and Taatjes, 2015; Deng et al., 2012; Jeronimo et al., 2016; Kagey et al., 2010; Mali…”
The Mediator complex: a central integrator of transcription
Allen, B. L., & Taatjes, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3951 · Cited by 922
Genome Architecture: Domain Organization of Interphase Chromosomes
Bickmore, W. A., & van Steensel, B. (2013) · Cell · doi:10.1016/j.cell.2013.02.001 · Cited by 725
Pott, S., & Lieb, J. D. (2014) · Nature Genetics · doi:10.1038/ng.3167 · Cited by 786
Eukaryotic core promoters and the functional basis of transcription initiation
Haberle, V., & Stark, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0028-8 · Cited by 774
CTCF Binding Polarity Determines Chromatin Looping
de Wit, E., Vos, E. S. M., Holwerda, S. J. B., Valdes-Quezada, C., Verstegen, M. J. A. M., Teunissen, H., Splinter, E., Wijchers, P. J., Krijger, P. H. L., & de Laat, W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.023 · Cited by 641
“Within TADs, chromatin loops can be formedbetween enhancers and distant target genes to increase their transcription (Deng et al., 2012).”
BackgroundThe 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 742
The Hierarchy of the 3D Genome
Gibcus, J. H., & Dekker, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.011 · Cited by 727
Enhancers as non-coding RNA transcription units: recent insights and future perspectives
Li, W., Notani, D., & Rosenfeld, M. G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.4 · Cited by 710
A Single Oncogenic Enhancer Rearrangement Causes Concomitant EVI1 and GATA2 Deregulation in Leukemia
Gröschel, S., Sanders, M. A., Hoogenboezem, R., de Wit, E., Bouwman, B. A. M., Erpelinck, C., van der Velden, V. H. J., Havermans, M., Avellino, R., van Lom, K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.019 · Cited by 687
Systematic mapping of functional enhancer–promoter connections with CRISPR interference
Fulco, C. P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S. R., Perez, E. M., Kane, M., Cleary, B., Lander, E. S., & Engreitz, J. M. (2016) · Science · doi:10.1126/science.aag2445 · Cited by 643
Developmental enhancers and chromosome topology
Furlong, E. E. M., & Levine, M. (2018) · Science · doi:10.1126/science.aau0320 · Cited by 641
Enhancers: 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 625
Three-dimensional genome architecture: players and mechanisms
Pombo, A., & Dillon, N. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3965 · Cited by 603
Transcription factors and 3D genome conformation in cell-fate decisions
Stadhouders, R., Filion, G. J. P., & Graf, T. (2019) · Nature · doi:10.1038/s41586-019-1182-7 · Cited by 530
Enhancer 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
CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation
Merkenschlager, M., & Nora, E. P. (2016) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-083115-022339 · Cited by 528
“Experimentally enforced interactions between the β-globin promoter and enhancers over 40 kb away can trigger transcription (21), providing a causal link between spatial interactions and gene expression.”
BackgroundTopology of mammalian developmental enhancers and their regulatory landscapes
de Laat, W., & Duboule, D. (2013) · Nature · doi:10.1038/nature12753 · Cited by 521
eRNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci
Mousavi, K., Zare, H., Dell’Orso, S., Grøntved, L., Gutierrez-Cruz, G., Derfoul, A., Hager, G. L., & Sartorelli, V. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.07.022 · Cited by 528
“Studies suggest that enhancers behave as modular platforms for assembly of long-range interactions in which transcription factors, chromatin regulators, cohesin/Mediator complex, and Pol II elevate gene transcription (Dean, 2006; Deng et al., 2012; Kagey et al., 2010; Li et al., 2012; Phillips-Cremins et al., 2013).”
Dynamic regulation of transcriptional states by chromatin and transcription factors
Voss, T. C., & Hager, G. L. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3623 · Cited by 504
Looping Back to Leap Forward: Transcription Enters a New Era
Levine, M., Cattoglio, C., & Tjian, R. (2014) · Cell · doi:10.1016/j.cell.2014.02.009 · Cited by 497
“Looping and activation depend on two key transcription factors, GATA1 and LDB1 (Deng et al., 2012).”
BackgroundGupta, R. M., Hadaya, J., Trehan, A., Zekavat, S. M., Roselli, C., Klarin, D., Emdin, C. A., Hilvering, C. R. E., Bianchi, V., Mueller, C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.049 · Cited by 450
“Chromatin loops regulate gene expression by positioning distal enhancers in proximity to target genes (Deng et al., 2012; Dowen et al., 2014).”
BackgroundThe 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
“In strong support of these models, experimental tethering between an enhancer and its target gene can induce gene transcription even in the absence of a key transcriptional activator (Deng et al. 2012).”
Reactivation of developmentally silenced globin genes by forced chromatin looping
Deng, W., Rupon, J. W., Krivega, I., Breda, L., Motta, I., Jahn, K. S., Reik, A., Gregory, P. D., Rivella, S., Dean, A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.050 · Cited by 443
“The ZFs targeting HS2 of the mouse LCR and the human g-globin promoters have been described previously (Deng et al., 2012; Gräslund et al., 2005).”
BackgroundMethodInfluentialSelf-citationThe 3D genome in transcriptional regulation and pluripotency
Gorkin, D. U., Leung, D., & Ren, B. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.05.017 · Cited by 391
Functional implications of genome topology
Cavalli, G., & Misteli, T. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2474 · Cited by 415
The Role of Chromosome Domains in Shaping the Functional Genome
Sexton, T., & Cavalli, G. (2015) · Cell · doi:10.1016/j.cell.2015.02.040 · Cited by 427
“…a recurring theme is the prevalence of homotypic or ‘‘like-with-like’’ interactions,whether this is thedimerization of proteinswithin chromatin loops (Deng et al., 2012), potential spatial networks of co-regulated genes (Schoenfelder et al., 2010) or a tendency for active and repressed chromatin…”
InfluentialTranscription factors LRF and BCL11A independently repress expression of fetal hemoglobin
Masuda, T., Wang, X., Maeda, M., Canver, M. C., Sher, F., Funnell, A. P. W., Fisher, C., Suciu, M., Martyn, G. E., Norton, L. J., et al. (2016) · Science · doi:10.1126/science.aad3312 · Cited by 373
The Spatial Organization of the Human Genome
Bickmore, W. A. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153515 · Cited by 391
The Hitchhiker’s guide to Hi-C analysis: Practical guidelines
Lajoie, B. R., Dekker, J., & Kaplan, N. (2014) · Methods · doi:10.1016/j.ymeth.2014.10.031 · Cited by 394
The Three-Dimensional Organization of Mammalian Genomes
Yu, M., & Ren, B. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060531 · Cited by 373
“…other genetic loci demonstrated that spatial proximity between promoters and distal enhancers due to chromatin looping is critical for transcriptional regulation of developmentally regulated gene expression (Deng et al. 2012, 2014; 16.2 Yu · Ren Review in Advance first posted on August 7, 2017.”
BackgroundInfluentialLive-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
Alexander, J. M., Guan, J., Li, B., Maliskova, L., Song, M., Shen, Y., Huang, B., Lomvardas, S., & Weiner, O. D. (2019) · eLife · doi:10.7554/elife.41769 · Cited by 346
On the existence and functionality of topologically associating domains
Beagan, J. A., & Phillips‐Cremins, J. E. (2020) · Nature Genetics · doi:10.1038/s41588-019-0561-1 · Cited by 381
Enhancer RNAs are an important regulatory layer of the epigenome
Sartorelli, V., & Lauberth, S. M. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0446-0 · Cited by 380
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
“Cells were infected with the MIGR-1 retrovirus expressing only GFP or mZFSA followed by an IRES element and GFP (Deng et al., 2012).”
BackgroundMethodInfluentialDecreased Enhancer-Promoter Proximity Accompanying Enhancer Activation
Benabdallah, N. S., Williamson, I., Illingworth, R. S., Kane, L., Boyle, S., Sengupta, D., Grimes, G. R., Therizols, P., & Bickmore, W. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.038 · Cited by 335
Stadhouders, R., Vidal, E., Serra, F., Stefano, B. D., Dily, F. L., Quilez, J., Gómez, A., Collombet, S., Berenguer, C., Cuartero, Y., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0030-7 · Cited by 362
The second decade of 3C technologies: detailed insights into nuclear organizationPreprint
Denker, A., & de Laat, W. L. (2016) · Genes & Development · doi:10.1101/gad.281964.116 · Cited by 357
“Artifi-cialrecruitmentofLdb1(oritsself-associationdomain only)viaanengineeredzincfingertothe β -globinpromoter appeared sufficient to not only re-establish the regulatory loop with the LCR but also strongly activate the recruited gene (Deng et al. 2012).”
Mechanisms of enhancer action: the known and the unknown
Panigrahi, A., & O’Malley, B. W. (2021) · Genome biology · doi:10.1186/s13059-021-02322-1 · Cited by 376
Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
Zhang, X., Choi, P. S., Francis, J. M., Imielinski, M. B., Watanabe, H., Cherniack, A. D., & Meyerson, M. M. (2015) · Nature Genetics · doi:10.1038/ng.3470 · Cited by 348
Genome-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
The origin of Metazoa: a unicellular perspective
Sebé-Pedrós, A., Degnan, B. M., & Ruiz-Trillo, I. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.21 · Cited by 332
Regulation of disease-associated gene expression in the 3D genome
Krijger, P. H. L., & de Laat, W. L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.138 · Cited by 332
LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice
Monahan, K. D., Horta, A., & Lomvardas, S. (2019) · Nature · doi:10.1038/s41586-018-0845-0 · Cited by 318
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
In Situ Capture of Chromatin Interactions by Biotinylated dCas9
Liu, X., Zhang, Y., Chen, Y., Li, M., Zhou, F., Li, K., Cao, H., Ni, M., Liu, Y., Gu, Z., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.003 · Cited by 318
The epigenetic basis of cellular heterogeneity
Carter, B. C., & Zhao, K. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00300-0 · Cited by 324
Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Phanstiel, D. H., Van Bortle, K., Spacek, D., Hess, G. T., Shamim, M. S., Machol, I., Love, M. I., Aiden, E. L., Bassik, M. C., & Snyder, M. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.006 · Cited by 299
Enhancer biology and enhanceropathies
Smith, E. R., & Shilatifard, A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2784 · Cited by 326
The Mediator complex as a master regulator of transcription by RNA polymerase II
Richter, W. F., Nayak, S., Iwasa, J., & Taatjes, D. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00498-3 · Cited by 343
Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism
Oldridge, D. A., Wood, A., Weichert‐Leahey, N., Crimmins, I., Sussman, R. T., Winter, C. L., McDaniel, L., Diamond, M. A., Hart, L. S., Zhu, S., et al. (2015) · Nature · doi:10.1038/nature15540 · Cited by 298
An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma
Drier, Y., Cotton, M. J., Williamson, K. E., Gillespie, S. M., Ryan, R. J. H., Kluk, M., Carey, C. D., Rodig, S. J., Sholl, L. M., Afrogheh, A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3502 · Cited by 306
Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping
Morgan, S. L., Mariano, N. C., Bermudez, A., Arruda, N. L., Wu, F., Luo, Y., Shankar, G., Jia, L., Chen, H., Hu, J.-F., et al. (2017) · Nature Communications · doi:10.1038/ncomms15993 · Cited by 279
Biology and Mechanisms of Action of the Vitamin D Hormone
Pike, J. W., & Christakos, S. (2017) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2017.07.001 · Cited by 292
Recent evidence that TADs and chromatin loops are dynamic structures
Hansen, A. S., Cattoglio, C., Darzacq, X., & Tjian, R. (2018) · Nucleus · doi:10.1080/19491034.2017.1389365 · Cited by 266
Bioinformatics and Drug Discovery
Xia, X. (2017) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026617666161116143440 · Cited by 264
The role of transcription in shaping the spatial organization of the genome
van Steensel, B., & Furlong, E. E. M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0114-6 · Cited by 247
El Khattabi, L., Zhao, H., Kalchschmidt, J., Young, N., Jung, S., Van Blerkom, P., Kieffer-Kwon, P., Kieffer-Kwon, K.-R., Park, S., Wang, X., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.011 · Cited by 244
“Experiments forcing P-E contacts demonstrate that such proximity is key to transcription (Deng et al., 2012; Morgan et al., 2017), but do not necessarily prove that stable loops are the norm.”
BackgroundDynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation
Goode, D. K., Obier, N., Vijayabaskar, M. S., Lie‐A‐Ling, M., Lilly, A. J., Hannah, R., Lichtinger, M., Batta, K., Florkowska, M., Patel, R., et al. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.01.024 · Cited by 239
“The latter mediates interactions between enhancer and promoter elements (Deng et al., 2012).”
Enhancer Function: Mechanistic and Genome-Wide Insights Come Together
Plank, J. L., & Dean, A. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.06.015 · Cited by 263
“Other studies suggest a role for enhancers in elongation (Sawado et al., 2003; Deng et al., 2012).”
Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9
Qin, P., Parlak, M., Kuscu, C., Bandaria, J. N., Mir, M., Szlachta, K. A., Singh, R., Darzacq, X., Yıldız, A., & Adli, M. (2017) · Nature Communications · doi:10.1038/ncomms14725 · Cited by 238
An Overview of Genome Organization and How We Got There: from FISH to Hi-C
Fraser, J., Williamson, I., Bickmore, W. A., & Dostie, J. (2015) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00006-15 · Cited by 232
“In one study, the Ldb1 protein complex composed of GATA-1, TAL1, LMO2, and Ldb1 was shown to mediate loop formation (221).”
BackgroundRegulatory Enhancer–Core-Promoter Communication via Transcription Factors and Cofactors
Zabidi, M. A., & Stark, A. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.10.003 · Cited by 228
Symmons, O., Pan, L., Remeseiro, S., Aktas, T., Klein, F., Huber, W., & Spitz, F. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.10.015 · Cited by 222
DeepC: predicting 3D genome folding using megabase-scale transfer learning
Schweßinger, R., Gosden, M. E., Downes, D. J., Brown, R. C., Oudelaar, A. M., Telenius, J. M., Teh, Y. W., Lunter, G. A., & Hughes, J. R. (2020) · Nature Methods · doi:10.1038/s41592-020-0960-3 · Cited by 223
Chromatin signatures of cancerPreprint
Morgan, M. A., & Shilatifard, A. (2015) · Genes & Development · doi:10.1101/gad.255182.114 · Cited by 218
“LDB1 is involved in the formation of chromatin loops in both Drosophila and mammalian cells and participates in enhancer–promoter communication (Morcillo et al. 1997; Deng et al. 2012; Krivega et al. 2014).”
BackgroundHBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers
Stadhouders, R., Aktuna, S., Thongjuea, S., Aghajanirefah, A., Pourfarzad, F., van IJcken, W. F. J., Lenhard, B., Rooks, H., Best, S., Menzel, S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71520 · Cited by 214
“These TFs are critical regulators of erythroid development (33, 35, 36), are positive regulators of murine Myb expression (26), and have been implicated in establishing long-range promoter-enhancer communication (37–40).”
Wei, 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 214
“Lastly, although long-range interactions alone can activate gene expression, that effect is reportedly minimal ( 15%) compared to normal activation levels (Deng et al., 2012).”
BackgroundInfluentialKim, W., Ludlow, A. T., Min, J., Robin, J. D., Stadler, G., Mender, I., Lai, T., Zhang, N., Wright, W. E., & Shay, J. W. (2016) · PLoS Biology · doi:10.1371/journal.pbio.2000016 · Cited by 223
Chromosomal Contact Permits Transcription between Coregulated Genes
Fanucchi, S., Shibayama, Y., Burd, S. C., Weinberg, M. S., & Mhlanga, M. M. (2013) · Cell · doi:10.1016/j.cell.2013.09.051 · Cited by 216
“One way that enhancer-promoter interactions are proposed to enhance transcription is by bringing protein complexes to the promoter (Deng et al., 2012; Gibcus and Dekker, 2013).”
Mechanisms of Interplay between Transcription Factors and the 3D Genome
Kim, S., & Shendure, J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.010 · Cited by 218
A Conserved Genetic Pathway Determines Inflorescence Architecture in Arabidopsis and Rice
Liu, C., Teo, Z. W. N., Bi, Y., Song, S., Xi, W., Yang, X., Yin, Z., & Yu, H. Q. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.02.013 · Cited by 201
Regulatory Landscaping: How Enhancer-Promoter Communication Is Sculpted in 3D
Robson, M. I., Ringel, A. R., & Mundlos, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.032 · Cited by 203
Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease
Hoban, M. D., Orkin, S. H., & Bauer, D. E. (2016) · Blood · doi:10.1182/blood-2015-09-618587 · Cited by 194
“The ability to program DNA-binding specificity of synthetic factors also allows for targeted gene regulation.(103) Expression of the selfassociationdomainofLdb1 (a transcription factor involved in chromatin looping of the LCR) linked to artificial zinc fingers recognizing the g-globin promoter in adult human erythrobl…”
BackgroundHistone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers
Yan, J., Chen, S.-A. A., Local, A., Liu, T., Qiu, Y., Lee, A. Y., Jung, I., Preißl, S., Rivera, C. M., Wang, C., et al. (2018) · Cell Research · doi:10.1038/cr.2018.1 · Cited by 198
Chromatin organization and transcriptional regulation
Hübner, M. R., Eckersley-Maslin, M. A., & Spector, D. L. (2012) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.11.006 · Cited by 186
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
Yang, J. H., & Hansen, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00710-6 · Cited by 191
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
“GATA-1 acts by recruiting its co-factor Lbd1, and tethering experiments have demonstrated that Lbd1 is responsible for bringing the LCR and promoter together [42].”
BackgroundPreformed chromatin topology assists transcriptional robustness of Shh during limb development
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
“Indeed, even though stable chromatin organization might ensure permanent enhancer–promoter communication, dynamic interactions were found to refine unspecific enhancer activities into more specific gene transcriptional output, and, consequently, their alterations were shown to cause gene misregulation (17, 45).”
BackgroundClustering of Tissue-Specific Sub-TADs Accompanies the Regulation of HoxA Genes in Developing Limbs
Berlivet, S., Paquette, D., Dumouchel, A., Langlais, D., Dostie, J., & Kmita, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1004018 · Cited by 170
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
Espinola, S. M., Götz, M., Bellec, M., Messina, O., Fiche, J.-B., Houbron, C., Dejean, M., Reim, I., Cardozo Gizzi, A. M., Lagha, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00816-z · Cited by 174
Enhancer Logic and Mechanics in Development and Disease
Rickels, R. A., & Shilatifard, A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.003 · Cited by 171
Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia
Yashiro–Ohtani, Y., Wang, H., Zang, C., Arnett, K. L., Bailis, W., Ho, Y., Knoechel, B., Lanauze, C. B., Louis, L., Forsyth, K. S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407079111 · Cited by 166
Thandapani, P. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.014 · Cited by 167
How subtle changes in 3D structure can create large changes in transcription
Xiao, J. Y., Hafner, A., & Boettiger, A. N. (2021) · eLife · doi:10.7554/elife.64320 · Cited by 162
Liu, J., Rutten, L., Limpens, E., van der Molen, T., van Velzen, R., Chen, R., Chen, Y., Geurts, R., Kohlen, W., Kulikova, O., et al. (2019) · The Plant Cell · doi:10.1105/tpc.18.00478 · Cited by 160
“It has been shown that gene activation by remote enhancers can be associated with chromatin loop formation thatbrings theenhancer incloseproximity to thepromoter, a process that can facilitate assembly of transcription complexes (Cook, 2003; Nolis et al., 2009; Deng et al., 2012).”
BackgroundIndependence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning
Ing-Simmons, E., Vaid, R., Bing, X. Y., Levine, M., Mannervik, M., & Vaquerizas, J. M. (2021) · Nature Genetics · doi:10.1038/s41588-021-00799-x · Cited by 159
The spatial organization of transcriptional control
Hafner, A., & Boettiger, A. N. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00526-0 · Cited by 158
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
Cubeñas-Potts, C., Rowley, M. J., Lyu, X., Li, G., Lei, E. P., & Corces, V. G. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1114 · Cited by 166
“The genes bound by inactive enhancers had significantly lower GROseq reads, consistent with the notion that a TSS– enhancer contact is necessary but not sufficient for transcriptional activation (Figure 4I) (66).”
BackgroundDOT1L 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
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
“Cat’s Cradling” the 3D Genome by the Act of LncRNA Transcription
Melé, M., & Rinn, J. L. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.011 · Cited by 152
The BET Protein BRD2 Cooperates with CTCF to Enforce Transcriptional and Architectural Boundaries
Hsu, S. C., Gilgenast, T. G., Bartman, C., Edwards, C. R., Stonestrom, A. J., Huang, P., Emerson, D. J., Evans, P., Werner, M. T., Keller, C. A., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.027 · Cited by 143
“3C 3C was performed as in (Deng et al., 2012).”
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
Metadata
- Authors
- Deng, W., Lee, J., Wang, H., Miller, J., Reik, A., Gregory, P. D., Dean, A., & Blobel, G. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- National Institutes of Health (US)
- Sangamo BioSciences (United States) (US)
- Corresponding author
- Blobel, Gerd A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 149
- Issue
- 6
- Pages
- 1233-1244
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3372860
- OpenAlex
- W1970831058
- Cited by
- 734
- References
- 49
- Citations by year
- 2026: 22 · 2025: 42 · 2024: 48 · 2023: 54 · 2022: 48 · 2021: 58 · 2020: 60 · 2019: 70 · 2018: 57 · 2017: 50 · 2016: 51 · 2015: 60 · 2014: 62 · 2013: 45 · 2012: 7
- FWCI
- 22.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL119479)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK058044, R01DK054937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin looping, locus control region, beta-globin promoter, LDB1, GATA-1, erythroid cells, enhancer-promoter interactions, RNA polymerase II phosphorylation, transcriptional activation
- MeSH terms
- Animals, Cell Line, Cell Separation, Chromatin, DNA-Binding Proteins, Embryo, Mammalian, Erythroblasts, Female, Gene Expression Regulation, Male, Promoter Regions, Genetic, Transcription, Genetic, Zinc Fingers, Protein Structure, Tertiary, GATA1 Transcription Factor, Mice, beta-Globins, LIM Domain Proteins
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
