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Super-Enhancers in the Control of Cell Identity and Disease
Open accessAbstract
Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. We produce a catalog of super-enhancers in a broad range of human cell types and find that super-enhancers associate with genes that control and define the biology of these cells. Interestingly, disease-associated variation is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes important in tumor pathogenesis. Thus, super-enhancers play key roles in human cell identity in health and in disease.
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“In mammals, cellular identity is established prenatally and maintained by H3K27ac-enriched super-enhancers (Hnisz et al., 2013; Whyte et al., 2013).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Hnisz et al., 2013
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
“The level of the active enhancer chromatin mark, H3K27ac, is not skewed in a similar manner towards these two locations, indicating that these regions are not super-enhancers”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Hnisz et al., 2013
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
“Super-enhancers commonly drive high-level expression of tissue-specific genes, including miRNA genes, with evolutionarily conserved cell type-specific function11–13.”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [13]
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
“SEs in both HCC and TAN were associated with GO terms related to metabolic genes (e.g. CYP3A4, SLC38A4, and IGFBP1) (Fig. 2c)20,21,58.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clusters of multiple enhancers, referred to as super enhancers, are particularly important in driving the expression of cell identity genes (6).”
From Brain cell type–specific enhancer–promoter interactome maps and disease - risk association (2019) · cites this paper as [6]
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“Many Hep‐IDCONNECT TFs, including NR1H3 and THRB, do not display typically used features to define hepatocyte identity TFs such as hepatocyte‐specific expression and association with super‐enhancers (Hnisz et al, 2013; Dubois et al, 2020a; Table EV3).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Hnisz et al, 2013
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In the citing paper
“Some enhancers reside in clusters of a handful116 to even hundreds (‘super enhancers’76,117), whereas many are solo.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [117]
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In the citing paper
“we detected binding of liver-restricted TFs (C/EBPα/β, HNF1A, and HNF4A), pioneering TFs (CEBPα/β, FOXA2, and FOXA3), and Wnt-signaling TFs (TCF7) at individual constituent enhancers (Fig. 3b)20,21.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredIn the citing paper
“suggesting that H3K27M participates in the formation of super enhancer-like elements purported to play a key role in cancer14.”
From Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas (2017) · cites this paper as [14]
In the citing paper
“This mystery, which we will call the enhancer-gene specificity conundrum, is important to solve because the majority of disease-associated non-coding variation occurs in the vicinity of enhancers and thus likely impacts these enhancers’ target genes (Ernst et al., 2011; Farh et al., 2015; Hnisz et al., 2013; Maurano et al., 2012).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2013
In the citing paper
“Tens of thousands of non-coding genetic variants have been linked with various human diseases and traits in genome-wide association studies (GWAS), and the majority of these variants occur in enhancers (Ernst et al., 2011; Farh et al., 2015; Hnisz et al., 2013; Maurano et al., 2012).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2013
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Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
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
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863
Topological 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
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
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Partitioning heritability by functional annotation using genome-wide association summary statistics
ReproGen Consortium, Finucane, H. K., Schizophrenia Working Group of the Psychiatric Genomics Consortium, The RACI Consortium, Bulik-Sullivan, B., Gusev, A., Trynka, G., Reshef, Y., Loh, P.-R., Anttila, V., et al. (2015) · Nature Genetics · doi:10.1038/ng.3404 · Cited by 2,604
“We did not see a large enrichment of super-enhancers vs. regular enhancers; the estimates for enrichment were 1.8x (s.e. 0 .2) for super-enhancers vs. 1.6x (s.e. 0 .1) for regular enhancers from the same paper [19] (denoted “H3K27ac (Hnisz)” in Figure 4).”
BackgroundMethodInfluentialCoactivator condensation at super-enhancers links phase separation and gene control
Sabari, B. R., Dall’Agnese, A., Boija, A., Klein, I. A., Coffey, E. L., Shrinivas, K., Abraham, B. J., Hannett, N. M., Zamudio, A. V., Manteiga, J. C., et al. (2018) · Science · doi:10.1126/science.aar3958 · Cited by 2,595
“SEs are established by the binding of master TFs to enhancer clusters (14, 15).”
BackgroundMethodInfluentialSelf-citationHoward, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0326-7 · Cited by 2,565
Long non-coding RNAs: definitions, functions, challenges and recommendations
Mattick, J. S., Amaral, P., Carninci, P., Carpenter, S. B., Chang, H. Y., Chen, L., Chen, R., Dean, C., Dinger, M. E., Fitzgerald, K. A., et al. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00566-8 · Cited by 2,509
Genetic and epigenetic fine mapping of causal autoimmune disease variants
Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., Shoresh, N., Whitton, H., Ryan, R. J. H., Shishkin, A. A., et al. (2015) · Nature · doi:10.1038/nature13835 · Cited by 1,956
Cohesin Loss Eliminates All Loop Domains
Rao, S. S. P., Huang, S.-C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K.-R., Sanborn, A. L., Johnstone, S. E., Bascom, G. D., Bochkov, I. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.026 · Cited by 1,883
“We also utilized an annotation of stitched and ranked (by H3K27Ac enrichment) superenhancers and enhancers from (Hnisz et al., 2013).”
BackgroundMethodNora, E. P., Goloborodko, A., Valton, A.-L., Gibcus, J. H., Uebersohn, A., Abdennur, N., Dekker, J., Mirny, L. A., & Bruneau, B. G. (2017) · Cell · doi:10.1016/j.cell.2017.05.004 · Cited by 1,709
“The super-enhancer list was retrieved from (Hnisz et al., 2013).”
A Phase Separation Model for Transcriptional Control
Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K., & Sharp, P. A. (2017) · Cell · doi:10.1016/j.cell.2017.02.007 · Cited by 1,753
Self-citationTOX transcriptionally and epigenetically programs CD8+ T cell exhaustion
Khan, O., Giles, J. R., McDonald, S., Manne, S., Ngiow, S. F., Patel, K. P., Werner, M. T., Huang, A. C., Alexander, K. A., Wu, J. E., et al. (2019) · Nature · doi:10.1038/s41586-019-1325-x · Cited by 1,646
Association analysis identifies 65 new breast cancer risk loci
Michailidou, K., Lindström, S., Dennis, J., Beesley, J., Hui, S., Kar, S., Lemaçon, A., Soucy, P., Glubb, D. M., Rostamianfar, A., et al. (2017) · Nature · doi:10.1038/nature24284 · Cited by 1,380
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307
Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
Ma, S., Zhang, B., LaFave, L. M., Earl, A. S., Chiang, Z., Hu, Y., Ding, J., Brack, A., Kartha, V. K., Tay, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.056 · Cited by 1,146
An environment-dependent transcriptional network specifies human microglia identity
Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., et al. (2017) · Science · doi:10.1126/science.aal3222 · Cited by 1,220
Transcriptional Addiction in Cancer
Bradner, J. E., Hnisz, D., & Young, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.12.013 · Cited by 1,221
“, 2014), focal amplification (Hnisz et al., 2013; Shi et al., 2013; Zhang et al., 2016b), and nucleation by small INDELs that create master TF binding sites (Mansour et al.”
InfluentialSelf-citationRegulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,163
“Recent genome-wide association studies of common polygenic autoimmune diseases have revealed that ∼60% of autoimmune-causal single-nucleotide polymorphisms (SNPs) are mapped to noncoding enhancer regions of immune cells (130–132), including cell type–specific superenhancers (132), and cell type–specific differentially…”
BackgroundActivation of proto-oncogenes by disruption of chromosome neighborhoods
Hnisz, D., Weintraub, A. S., Day, D. S., Valton, A.-L., Bak, R. O., Li, C. H., Goldmann, J., Lajoie, B. R., Fan, Z. P., Sigova, A. A., et al. (2016) · Science · doi:10.1126/science.aad9024 · Cited by 1,042
“Active oncogenes are often associated with super-enhancers (17, 18), and we found that 13 of the 27 active T-ALL Pathogenesis Genes associated with super-enhancers (Fig.”
BackgroundSelf-citationThe selection and function of cell type-specific enhancers
Heinz, S., Romanoski, C. E., Benner, C., & Glass, C. K. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3949 · Cited by 1,010
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes
Dowen, J. M., Fan, Z. P., Hnisz, D., Ren, G., Abraham, B. J., Zhang, L. N., Weintraub, A. S., Schuijers, J., Lee, T. I., Zhao, K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.030 · Cited by 884
Self-citationEver-Changing Landscapes: Transcriptional Enhancers in Development and Evolution
Long, H. K., Prescott, S. L., & Wysocka, J. (2016) · Cell · doi:10.1016/j.cell.2016.09.018 · Cited by 945
“Indeed, key lineage genes in a given cell type tend to be associated with dense cluster(s) of highly active enhancers, often referred to as super-enhancers (Hnisz et al., 2013; Whyte et al., 2013).”
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Allen, B. L., & Taatjes, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3951 · Cited by 922
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Lasko, L. M., Jakob, C. G., Edalji, R. P., Qiu, W., Montgomery, D., Digiammarino, E. L., Hansen, T. M., Risi, R. M., Frey, R., Manaves, V., et al. (2017) · Nature · doi:10.1038/nature24028 · Cited by 858
Getting up to speed with transcription elongation by RNA polymerase II
Jonkers, I., & Lis, J. T. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3953 · Cited by 876
A compendium of chromatin contact maps reveals spatially active regions in the human genome
Schmitt, A. D., Hu, M., Jung, I., Xu, Z., Qiu, Y., Tan, C. L., Li, Y., Lin, S., Lin, Y., Barr, C. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.061 · Cited by 866
“(C) Bar plot showing the observed overlap between actual FIRE bins and previously characterized typical enhancers (blue) (Hnisz et al., 2013) for each available cell line or tissue that has both Hi-C data and typical enhancer calls.”
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Kwiatkowski, N. P., Zhang, T., Rahl, P. B., Abraham, B. J., Reddy, J., Ficarro, S. B., Dastur, A., Amzallag, A., Ramaswamy, S., Tesar, B. M., et al. (2014) · Nature · doi:10.1038/nature13393 · Cited by 865
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David, C. J., & Massagué, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0007-0 · Cited by 851
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Nott, A., Holtman, I. R., Coufal, N. G., Schlachetzki, J. C. M., Yu, M., Hu, R., Han, C. Z., Pena, M., Xiao, J., Wu, Y., et al. (2019) · Science · doi:10.1126/science.aay0793 · Cited by 699
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Self-citationPott, S., & Lieb, J. D. (2014) · Nature Genetics · doi:10.1038/ng.3167 · Cited by 786
CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells
Liu, S. J., Horlbeck, M. A., Cho, S. W., Birk, H. S., Malatesta, M., He, D. X., Attenello, F. J., Villalta, J. E., Cho, M. Y., Chen, Y., et al. (2016) · Science · doi:10.1126/science.aah7111 · Cited by 756
Long Noncoding RNAs in Cardiovascular Diseases
Uchida, S., & Dimmeler, S. (2015) · Circulation Research · doi:10.1161/circresaha.116.302521 · Cited by 746
Structural variation in the 3D genome
Spielmann, M., Lupiáñez, D. G., & Mundlos, S. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0007-0 · Cited by 746
Xiang, J., Yin, Q.-F., Chen, T., Zhang, Y., Zhang, X.-O., Wu, Z., Zhang, S., Wang, H., Ge, J., Lu, X., et al. (2014) · Cell Research · doi:10.1038/cr.2014.35 · Cited by 744
Liquid–liquid phase separation in human health and diseases
Wang, B., Zhang, L., Dai, T., Qin, Z., Lu, H., Zhang, L., & Zhou, F. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00678-1 · Cited by 784
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BackgroundBRD4 and Cancer: going beyond transcriptional regulation
Donati, B., Lorenzini, E., & Ciarrocchi, A. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0915-9 · Cited by 742
“Genome-wide studies indicated that SEs mark lineage specific TFs and oncogenes in a wide range of cancer type, revealing that these structures are acquired during tumorigenesis and are unique to cancer cells while largely absent in untrasformed cells [7, 53, 54].”
BackgroundMorán, S., Arribas, C., & Esteller, M. (2015) · Epigenomics · doi:10.2217/epi.15.114 · Cited by 721
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Schultz, M. D., He, Y., Whitaker, J. W., Hariharan, M., Mukamel, E. A., Leung, D., Rajagopal, N., Nery, J. R., Urich, M. A., Chen, H., et al. (2015) · Nature · doi:10.1038/nature14465 · Cited by 690
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Yang, J.-H., Hayano, M., Griffin, P. T., Amorim, J. A., Bonkowski, M. S., Apostolides, J. K., Salfati, E. L., Blanchette, M., Munding, E. M., Bhakta, M., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.027 · Cited by 643
Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma
Northcott, P. A., Lee, C., Zichner, T., Stütz, A. M., Erkek, S., Kawauchi, D., Shih, D. J. H., Hovestadt, V., Zapatka, M., Sturm, D., et al. (2014) · Nature · doi:10.1038/nature13379 · Cited by 642
CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer
Chipumuro, E., Marco, E., Christensen, C. L., Kwiatkowski, N. P., Zhang, T., Hatheway, C. M., Abraham, B. J., Sharma, B., Yeung, C. M., Altabef, A. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.024 · Cited by 631
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Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Shu, S., Lin, C. Y., He, H. H., Witwicki, R. M., Tabassum, D. P., Roberts, J. M., Janiszewska, M., Jin Huh, S., Liang, Y., Ryan, J., et al. (2016) · Nature · doi:10.1038/nature16508 · Cited by 632
“3d and Supplementary Table 3) 8,9,12,13 .”
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Brown, J. D., Lin, C. Y., Duan, Q., Griffin, G., Federation, A. J., Paranal, R. M., Bair, S., Newton, G., Lichtman, A. H., Kung, A. L., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.024 · Cited by 614
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BOCS, Michailidou, K., kConFab Investigators, AOCS Group, NBCS, GENICA Network, Beesley, J., Lindström, S., Canisius, S., Dennis, J., et al. (2015) · Nature Genetics · doi:10.1038/ng.3242 · Cited by 598
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23andMe Research Team, Ferreira, M. A., collaborators, A., BIOS consortium, Study, L. C., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., et al. (2017) · Nature Genetics · doi:10.1038/ng.3985 · Cited by 550
“…(based on 5C34, promoter capture Hi-C35, ChIA-PET36 or in situ Hi-C37 data), but also an association between variation in enhancer epigenetic marks and variation in gene transcription levels (based on PreSTIGE38, H3K27ac enhancer and super-enhancer annotation 39, IM-PET40 or FANTOM541 analyses).”
Johann, P. D., Erkek, S., Zapatka, M., Kerl, K., Buchhalter, I., Hovestadt, V., Jones, D., Sturm, D., Hermann, C., Segura‐Wang, M., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.02.001 · Cited by 586
“domains (Hnisz et al., 2013), andmay play an essential role in establishing cell identity.”
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Liu, X., Wang, Y., Lu, H., Li, J., Yan, X., Xiao, M., Hao, J., Alekseev, A., Khong, H., Chen, T., et al. (2019) · Nature · doi:10.1038/s41586-019-0979-8 · Cited by 533
Mechanisms of Jak/STAT Signaling in Immunity and Disease
Villarino, A. V., Kanno, Y., Ferdinand, J. R., & O’Shea, J. J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401867 · Cited by 564
Neuroblastoma is composed of two super-enhancer-associated differentiation states
van Groningen, T., Köster, J., Valentijn, L. J., Zwijnenburg, D. A., Akogul, N., Hasselt, N. E., Broekmans, M. E. C., Haneveld, F., Nowakowska, N. E., Bras, J., et al. (2017) · Nature Genetics · doi:10.1038/ng.3899 · Cited by 556
Glioma epigenetics: From subclassification to novel treatment options
Gusyatiner, O., & Hegi, M. E. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.010 · Cited by 556
Absence of a simple code: how transcription factors read the genome
Slattery, M., Zhou, T., Yang, L., Dantas Machado, A. C., Gordân, R., & Rohs, R. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.07.002 · Cited by 537
Joint Analysis of Functional Genomic Data and Genome-wide Association Studies of 18 Human Traits
Pickrell, J. K. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.004 · Cited by 526
H3K4me3 breadth is linked to cell identity and transcriptional consistency
Benayoun, B. A., Pollina, E. A., Ucar, D., Mahmoudi, S., Karra, K., Wong, E. D., Devarajan, K., Daugherty, A. C., Kundaje, A. B., Mancini, E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.027 · Cited by 536
Guo, S., Diep, D. H., Plongthongkum, N., Fung, H.-L., Zhang, K., & Zhang, K. (2017) · Nature Genetics · doi:10.1038/ng.3805 · Cited by 528
A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC
Mohammad, H. P., Smitheman, K. N., Kamat, C. D., Soong, D., Federowicz, K., Aller, G. S. V., Schneck, J., Carson, J. D., Liu, Y., Butticello, M., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.06.002 · Cited by 521
“Treatment with GSK2879552 increased LSD1 signal enrichment at both SCLC specific typical and super enhancers (Figure 3J), as previously defined in NCI-H2171 cells (Hnisz et al., 2013).”
BackgroundResultEpigenetic control of CD8+ T cell differentiation
Henning, A. N., Roychoudhuri, R., & Restifo, N. P. (2018) · Nature reviews. Immunology · doi:10.1038/nri.2017.146 · Cited by 518
Borromeo, M. D., Savage, T. K., Kollipara, R. K., He, M. Y., Augustyn, A., Osborne, J. K., Girard, L., Minna, J. D., Gazdar, A. F., Cobb, M. H., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.081 · Cited by 502
“, 2014), and the low percentage of super-enhancers common between the subtypes is in the range seen between lineally unrelated cells (Hnisz et al., 2013) (Table S6).”
InfluentialPartitioning of cancer therapeutics in nuclear condensates
Klein, I. A., Boija, A., Afeyan, L. K., Hawken, S. W., Fan, M., Dall’Agnese, A., Oksuz, O., Henninger, J. E., Shrinivas, K., Sabari, B. R., et al. (2020) · Science · doi:10.1126/science.aaz4427 · Cited by 510
Self-citationParkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
Soldner, F., Stelzer, Y., Shivalila, C., Abraham, B. J., Latourelle, J. C., Barrasa, M. I., Goldmann, J. E., Myers, R. H., Young, R. A., & Jaenisch, R. (2016) · Nature · doi:10.1038/nature17939 · Cited by 507
Self-citationZhang, H., Ahearn, T. U., Lecarpentier, J., Barnes, D. R., Beesley, J., Jiang, X., O’Mara, T. A., Qi, G., Zhao, N., Bolla, M. K., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0609-2 · Cited by 499
Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries
Boeva, V., Louis‐Brennetot, C., Peltier, A., Durand, S., Pierre‐Eugène, C., Raynal, V., Etchevers, H., Thomas, S., Lermine, A., Daudigeos‐Dubus, E., et al. (2017) · Nature Genetics · doi:10.1038/ng.3921 · Cited by 516
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
Transcription factor trapping by RNA in gene regulatory elements
Sigova, A. A., Abraham, B. J., Ji, X., Molinie, B., Hannett, N. M., Guo, Y. E., Jangi, M., Giallourakis, C. C., Sharp, P. A., & Young, R. A. (2015) · Science · doi:10.1126/science.aad3346 · Cited by 492
Self-citationOverview of Histone Modification
Zhang, Y., Sun, Z., Jia, J., Du, T., Zhang, N., Tang, Y., Fang, Y., & Fang, D. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-8104-5_1 · Cited by 530
Cancer epigenetics: Moving forward
Nebbioso, A., Tambaro, F. P., Dell’Aversana, C., & Altucci, L. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007362 · Cited by 500
Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas
Piunti, A., Hashizume, R., Morgan, M. A., Bartom, E. T., Horbinski, C. M., Marshall, S. A., Rendleman, E. J., Ma, Q., Takahashi, Y.-H., Woodfin, A. R., et al. (2017) · Nature Medicine · doi:10.1038/nm.4296 · Cited by 445
CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer
Wang, Y., Zhang, T., Kwiatkowski, N. P., Abraham, B. J., Lee, T. I., Xie, S., Yuzugullu, H., Von, T., Li, H., Lin, Z., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.063 · Cited by 464
“Previous work has shown that super-enhancers concentrate components of the transcriptional apparatus to drive high-level expression of their target genes (Hnisz et al., 2013; Lovén et al., 2013; Whyte et al., 2013).”
Self-citationBET Proteins as Targets for Anticancer Treatment
Stathis, A., & Bertoni, F. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0605 · Cited by 463
Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers
Hnisz, D., Schuijers, J., Lin, C. Y., Weintraub, A. S., Abraham, B. J., Lee, T. I., Bradner, J. E., & Young, R. A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.014 · Cited by 476
Self-citationRole of non-coding sequence variants in cancer
Khurana, E., Fu, Y., Chakravarty, D., Demichelis, F., Rubin, M. A., & Gerstein, M. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2015.17 · Cited by 459
RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity
Pefanis, E., Wang, J., Rothschild, G., Lim, J., Kazadi, D., Sun, J., Federation, A., Chao, J., Elliott, O., Liu, Z.-P., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.034 · Cited by 464
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Schaub, F. X., Dhankani, V., Berger, A. C., Trivedi, M., Richardson, A. B., Shaw, R., Zhao, W., Zhang, X., Ventura, A., Liu, Y., et al. (2018) · Cell Systems · doi:10.1016/j.cels.2018.03.003 · Cited by 431
Huang, S., Li, X., Zheng, H., Si, X., Li, B., Wei, G., Li, C., Chen, Y., Chen, Y., Liao, W., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.038361 · Cited by 454
Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451
MYC Deregulation in Primary Human Cancers
Kalkat, M., Melo, J. D., Hickman, K. A., Lourenco, C., Redel, C., Resetca, D., Tamachi, A., Tu, W. B., & Penn, L. Z. (2017) · Genes · doi:10.3390/genes8060151 · Cited by 469
“This concept has already been highlighted by the discovery and use of the small molecule JQ1 as an inhibitor of MYC expression in malignancies where MYC expression is regulated by large enhancers, such as in MM [128,134].”
BackgroundMapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler
Chen, Y., Zhang, Y., Wang, Y., Zhang, L., Brinkman, E. K., Adam, S. A., Goldman, R. D., van Steensel, B., Ma, J., & Belmont, A. S. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201807108 · Cited by 435
The 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
Liquid–liquid phase separation drives cellular function and dysfunction in cancer
Mehta, S., & Zhang, J. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00444-7 · Cited by 464
Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor
Christensen, C. L., Kwiatkowski, N. P., Abraham, B. J., Carretero, J., Al‐Shahrour, F., Zhang, T., Chipumuro, E., Herter-Sprie, G. S., Akbay, E. A., Altabef, A. B., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.10.019 · Cited by 446
Self-citationThe Nature of Embryonic Stem Cells
Martello, G., & Smith, A. G. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013116 · Cited by 444
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415
“For example, in embryonic stem cells (ESC), exceptionally large stretches of H3K27Ac-marked regulatory elements, termed super-enhancers (SE), are associated with genes that play prominent roles in ESC self-renewal (37, 38).”
InfluentialAdvances in Targeting ‘Undruggable’ transcription Factors With Small Molecules
Henley, M. J., & Koehler, A. N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00199-0 · Cited by 409
Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
ABCTB Investigators, Milne, R. L., EMBRACE, Collaborators, G. S., HEBON, kConFab/AOCS Investigators, Collaborators, N., Kuchenbaecker, K. B., Michailidou, K., Beesley, J., et al. (2017) · Nature Genetics · doi:10.1038/ng.3785 · Cited by 415
Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control
Hnisz, D., Day, D. S., & Young, R. A. (2016) · Cell · doi:10.1016/j.cell.2016.10.024 · Cited by 420
“…the enhancergene specificity conundrum, is important to solve because the majority of disease-associated non-coding variation occurs in the vicinity of enhancers and thus likely impacts these enhancers’ target genes (Ernst et al., 2011; Farh et al., 2015; Hnisz et al., 2013; Maurano et al., 2012).”
Self-citationPhase separation of YAP reorganizes genome topology for long-term YAP target gene expression
Cai, D., Feliciano, D., Dong, P., Flores, E., Gruebele, M., Porat‐Shliom, N., Sukenik, S., Liu, Z. J., & Lippincott‐Schwartz, J. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0433-z · Cited by 426
CD4 + T-cell subsets in inflammatory diseases: beyond the T h 1/T h 2 paradigm
Hirahara, K., & Nakayama, T. (2016) · International Immunology · doi:10.1093/intimm/dxw006 · Cited by 417
YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers
Stein, C., Bardet, A. F., Roma, G., Bergling, S., Clay, I., Ruchti, A., Agarinis, C., Schmelzle, T., Bouwmeester, T., Schübeler, D., et al. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1005465 · Cited by 414
The PRACTICAL Consortium, Day, F. R., kConFab Investigators, AOCS Investigators, Scotland, G., EPIC-InterAct Consortium, Study, L. C., Ruth, K. S., Thompson, D. J., Lunetta, K. L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3412 · Cited by 402
Modulating biomolecular condensates: a novel approach to drug discovery
Mitrea, D. M., Mittasch, M., Gomes, B. F., Klein, I. A., & Murcko, M. A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00505-4 · Cited by 434
Mediator kinase inhibition further activates super-enhancer-associated genes in AML
Pelish, H. E., Liau, B. B., Nitulescu, I. I., Tangpeerachaikul, A., Poss, Z. C., Silva, D. H. D., Caruso, B., Arefolov, A., Fadeyi, O., Christie, A. L., et al. (2015) · Nature · doi:10.1038/nature14904 · Cited by 406
“CDK12(714-1063):CycK(1-267) and CDK13(694-1039):CycK (1-267) were expressed in insect cells and used at ~500 nM per reaction.”
3D 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
“…of diseaseassociated single nucleotide polymorphisms (SNPs) showed that they tend to occur in proximity to enhancers, as observed previously (Hnisz et al., 2013; Maurano et al., 2012), but were not enriched in CTCF-CTCF loop anchor regions that lack evidence of local enhancer activity…”
Self-citationWeischenfeldt, J., Dubash, T., Drainas, A. P., Mardin, B. R., Chen, Y., Stütz, A. M., Waszak, S. M., Bosco, G., Halvorsen, A. R., Raeder, B., et al. (2017) · Nature Genetics · doi:10.1038/ng.3722 · Cited by 404
Herranz, D., Ambesi-Impiombato, A., Palomero, T., Schnell, S. A., Belver, L., Wendorff, A. A., Xu, L., Castillo-Martin, M., Llobet-Navás, D., Cordon-Cardo, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3665 · Cited by 405
Metadata
- Authors
- Hnisz, D., Abraham, B. J., Lee, T. I., Lau, A., Saint-André, V., Sigova, A. A., Hoke, H. A., & Young, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Young, Richard A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 155
- Issue
- 4
- Pages
- 934-947
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3841062
- OpenAlex
- W2004966039
- Cited by
- 3,662
- References
- 164
- Citations by year
- 2026: 182 · 2025: 294 · 2024: 332 · 2023: 321 · 2022: 360 · 2021: 406 · 2020: 331 · 2019: 315 · 2018: 291 · 2017: 259 · 2016: 232 · 2015: 215 · 2014: 110 · 2013: 5
- FWCI
- 83.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- University of California
- National Institutes of Health (CA146445, HG002668, CA109901, P30AG10161, R01AG36042, R01AG17917, RC2AG36547)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- super-enhancers, enhancers, cell identity, transcription factors, chromatin regulators, embryonic stem cells, oncogenes, cancer, enhancer transcription, human cell types
- MeSH terms
- Animals, Chromatin, Enhancer Elements, Genetic, Humans, Neoplasms, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Polymorphism, Single Nucleotide, Embryonic Stem Cells
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