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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
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“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]
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“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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“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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Items 101–200 of 1,018
The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers
Alver, B. H., Kim, K. H., Lu, P., Wang, X., Manchester, H. E., Wang, W., Haswell, J. R., Park, P. J., & Roberts, C. W. M. (2017) · Nature Communications · doi:10.1038/ncomms14648 · Cited by 427
Grajales‐Reyes, G. E., Iwata, A., Albring, J. C., Wu, X., Tussiwand, R., Wumesh, K. C., Kretzer, N. M., Briseño, C. G., Durai, V., Bagadia, P., et al. (2015) · Nature Immunology · doi:10.1038/ni.3197 · Cited by 398
dbSUPER: a database of super-enhancers in mouse and human genome
Khan, A., & Zhang, X. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1002 · Cited by 392
A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
Kaufman, C. K., Mosimann, C., Fan, Z. P., Yang, S. P., Thomas, A. J., Ablain, J., Tan, J. L., Fogley, R. D., van Rooijen, E., Hagedorn, E. J., et al. (2016) · Science · doi:10.1126/science.aad2197 · Cited by 403
“Examining multiple normal and cancer cell types (66 and 18 types, respectively), the enrichment of H3K27Ac signal at SOX10 was significant and specific to melanoma cells, hNCC’s, and brain tissue, which contains SOX10-expressing oligodendrocytes (Fig 4E) (26).”
BackgroundMethodInfluentialSelf-citationTranscriptional Dependencies in Diffuse Intrinsic Pontine Glioma
Nagaraja, S., Vitanza, N. A., Woo, P. J., Taylor, K. R., Liu, F., Zhang, L., Li, M., Meng, W., Ponnuswami, A., Sun, W., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.03.011 · Cited by 400
“The genes associated with SEs in cancer are enriched for drivers of oncogenic state as well as normal regulators of cell identity (Lovén et al., 2013; Hnisz et al., 2013).”
BackgroundTowards a comprehensive catalogue of validated and target-linked human enhancers
Gasperini, M., Tome, J. M., & Shendure, J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0209-0 · Cited by 396
Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition
Álvarez‐Fernández, M., & Malumbres, M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.010 · Cited by 399
The role of enhancers in cancer
Sur, I., & Taipale, J. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.62 · Cited by 393
An atlas of dynamic chromatin landscapes in mouse fetal development
Gorkin, D. U., Barozzi, I., Zhao, Y., Zhang, Y., Huang, H., Lee, A. Y., Li, B., Chiou, J., Wildberg, A., Ding, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2093-3 · Cited by 374
Benayoun, B. A., Pollina, E. A., Singh, P. P., Mahmoudi, S., Harel, I., Casey, K. M., Dulken, B. W., Kundaje, A., & Brunet, A. (2019) · Genome Research · doi:10.1101/gr.240093.118 · Cited by 360
The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications
Leonard, W. J., Lin, J., & O’Shea, J. J. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.028 · Cited by 385
Jiang, X., O’Reilly, P. F., Aschard, H., Hsu, Y., Richards, J. B., Dupuis, J., Ingelsson, E., Karasik, D., Pilz, S., Berry, D. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02662-2 · Cited by 389
Genetic dissection of the α-globin super-enhancer in vivo
Hay, D., Hughes, J. R., Babbs, C., Davies, J. O. J., Graham, B. J., Hanssen, L. L. P., Kassouf, M. T., Oudelaar, A. M., Sharpe, J. A., Suciu, M. C., et al. (2016) · Nature Genetics · doi:10.1038/ng.3605 · Cited by 385
Shi, W., Liao, Y., Willis, S. N., Taubenheim, N., Inouye, M., Tarlinton, D. M., Smyth, G. K., Hodgkin, P. D., Nutt, S. L., & Corcoran, L. M. (2015) · Nature Immunology · doi:10.1038/ni.3154 · Cited by 397
Active medulloblastoma enhancers reveal subgroup-specific cellular origins
Lin, C. Y., Erkek, S., Tong, Y., Yin, L., Alexander Joel Federation, Zapatka, M., Haldipur, P., Kawauchi, D., Risch, T., Warnatz, H.-J., et al. (2016) · Nature · doi:10.1038/nature16546 · Cited by 382
Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment
Kitagawa, Y., Ohkura, N., Kidani, Y., Vandenbon, A., Hirota, K., Kawakami, R., Yasuda, K., Motooka, D., Nakamura, S., Kondo, M., et al. (2016) · Nature Immunology · doi:10.1038/ni.3646 · Cited by 390
SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis
Muhar, M., Ebert, A., Neumann, T., Umkehrer, C., Jude, J., Wieshofer, C., Rescheneder, P., Lipp, J., Herzog, V. A., Reichholf, B., et al. (2018) · Science · doi:10.1126/science.aao2793 · Cited by 371
Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice
Adam, R. C., Yang, H., Rockowitz, S., Larsen, S. B., Nikolova, M., Oristian, D., Polak, L., Kadaja, M., Asare, A., Zheng, D., et al. (2015) · Nature · doi:10.1038/nature14289 · Cited by 371
Super-enhancers delineate disease-associated regulatory nodes in T cells
Vahedi, G., Kanno, Y., Furumoto, Y., Jiang, K., Parker, S. C. J., Erdos, M. R., Davis, S. R., Roychoudhuri, R., Restifo, N. P., Gadina, M., et al. (2015) · Nature · doi:10.1038/nature14154 · Cited by 369
Chen, K., Chen, Z., Wu, D., Zhang, L., Lin, X., Su, J., Rodriguez, B., Xi, Y., Xia, Z., Chen, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3385 · Cited by 373
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation
Wang, X., Lee, R. S., Alver, B., Haswell, J. R., Wang, S., Mieczkowski, J., Drier, Y., Gillespie, S. M., Archer, T. C., Wu, J. N., et al. (2016) · Nature Genetics · doi:10.1038/ng.3746 · Cited by 376
“Super-enhancers – large clusters of enhancers with high cumulative H3K27ac levels 17,18 – have recently been implicated as controlling genes central to maintaining cell identity and, in cancer, genes underlying the malignant state 17,18 .”
Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement
Kline, A. D., Moss, J. F., Selicorni, A., Bisgaard, A., Deardorff, M. A., Gillett, P. M., Ishman, S. L., Kerr, L. M., Levin, A. V., Mulder, P. A., et al. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0031-0 · Cited by 392
Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single Cells
Xie, S., Duan, J., Li, B., Zhou, P., & Hon, G. C. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.03.007 · Cited by 334
“Consistent with previous observations of RNAPII binding at enhancers and super-enhancers (Hnisz et al., 2013), we found that RNAPII binding is among the strongest features of the KRAB-responsive enhancers identified by Mosaic-seq.”
BackgroundTranscription factor binding dynamics during human ES cell differentiation
Tsankov, A. M., Gu, H., Akopian, V., Ziller, M. J., Donaghey, J., Amit, I., Gnirke, A., & Meissner, A. (2015) · Nature · doi:10.1038/nature14233 · Cited by 358
Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples
Jin, W., Tang, Q., Wan, M., Cui, K., Zhang, Y., Ren, G., Ni, B., Sklar, J., Przytycka, T. M., Childs, R., et al. (2015) · Nature · doi:10.1038/nature15740 · Cited by 332
“Super-enhancers play a key role in regulating expression of critical cell-specific genes 14–16 .”
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas
Clark, V. E., Harmancı, A. S., Bai, H., Youngblood, M. W., Lee, T. I., Baranoski, J. F., Ercan‐Sencicek, A. G., Abraham, B. J., Weintraub, A. S., Hnisz, D., et al. (2016) · Nature Genetics · doi:10.1038/ng.3651 · Cited by 356
Self-citationOhkura, N., & Sakaguchi, S. (2020) · Cell Research · doi:10.1038/s41422-020-0324-7 · Cited by 374
Melin, B. S., Barnholtz‐Sloan, J. S., Wrensch, M., Johansen, C., Il’yasova, D., Kinnersley, B., Ostrom, Q. T., Labrèche, K., Chen, Y., Armstrong, G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3823 · Cited by 351
Super-Enhancer-Driven Transcriptional Dependencies in Cancer
Sengupta, S., & George, R. E. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.03.006 · Cited by 354
“The SEs associated with key oncogenes are unique to cancer cells and conspicuously absent in [331_TD$DIFF]untransformed cells of identical lineage, suggesting that they are acquired during the course of tumorigenesis and underlie the oncogenic state in fundamental ways [17].”
BackgroundResultInfluentialThe long noncoding RNA Wisper controls cardiac fibrosis and remodeling
Micheletti, R., Plaisance, I., Abraham, B. J., Sarre, A., Ting, C.-C., Alexanian, M., Maric, D., Maison, D., Nemir, M., Young, R. A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai9118 · Cited by 358
Self-citationSuboptimization of developmental enhancers
Farley, E. K., Olson, K. M., Zhang, W., Brandt, A. J., Rokhsar, D. S., & Levine, M. S. (2015) · Science · doi:10.1126/science.aac6948 · Cited by 319
Widespread transcriptional pausing and elongation control at enhancers
Henriques, T., Scruggs, B. S., Inouye, M. O., Muse, G. W., Williams, L. H., Burkholder, A. B., Lavender, C. A., Fargo, D. C., & Adelman, K. (2018) · Genes & Development · doi:10.1101/gad.309351.117 · Cited by 350
“Large clusters of enhancers, called superenhancers, have been identified previously in a number of mammalian cell types, sur- rounding genes important for cell identity and disease (Hnisz et al. 2013; Whyte et al. 2013).”
BackgroundMethodInfluentialIdentification 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
“MYC overexpression has been observed as a consequence of rearrangements with the IgH locus in Burkitts lymphoma 22,49 (Fig.”
InfluentialFunctional Enhancers Shape Extrachromosomal Oncogene Amplifications
Morton, A. R., Dogan-Artun, N., Faber, Z. J., MacLeod, G. D. A. H., Bartels, C. F., Piazza, M. S., Allan, K. C., Mack, S. C., Wang, X., Gimple, R. C., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.039 · Cited by 336
“Compared to their normal counterparts, tumor cells frequently show locus-specific gains and losses of typical- and super-enhancer activity across the epigenome (Akhtar-Zaidi et al., 2012; Hnisz et al., 2013).”
BackgroundArchitectural and Functional Commonalities between Enhancers and Promoters
Kim, T.-K., & Shiekhattar, R. (2015) · Cell · doi:10.1016/j.cell.2015.08.008 · Cited by 354
Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development
Anderson, K. M., Anderson, D. M., McAnally, J., Shelton, J. M., Bassel‐Duby, R., & Olson, E. N. (2016) · Nature · doi:10.1038/nature20128 · Cited by 334
Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing
Teng, F., Chen, Y., Xiao, T., Li, W., Cato, L., Zhang, P., Cotter, M. B., Bowden, M., Lis, R. T., Zhao, S. G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617467114 · Cited by 338
“Moreover, recent studies suggested that superenhancer-associated genes tend to be functionally important in the control of cell identity and disease (27).”
BackgroundLoci associated with skin pigmentation identified in African populations
Crawford, N. G., Kelly, D. E., Hansen, M. E. B., Beltrame, M. H., Fan, S., Bowman, S. L., Jewett, E., Ranciaro, A., Thompson, S., Lo, Y., et al. (2017) · Science · doi:10.1126/science.aan8433 · Cited by 321
“3), suggesting that this regionmay regulate expression of genes critical to melanocyte function (31).”
Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.003 · Cited by 320
“Clusters of H3K27acmarked enhancers form super-enhancers (SE), which tend to regulate genes that orchestrate cell fate and lineage commitment, and frequently become hijacked during oncogenic transformation (Hnisz et al., 2013; Zhang et al., 2016).”
BackgroundMicroenvironmental Determinants of Pancreatic Cancer
Heßmann, E., Buchholz, S., Demir, İ. E., Singh, S. K., Gress, T. M., Ellenrieder, V., & Neeße, A. (2020) · Physiological Reviews · doi:10.1152/physrev.00042.2019 · Cited by 336
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
“For example, the extensively studied regulatory sequences of the immunoglobulin heavy chain enhancer (the first mammalian enhancer discovered) 7–9 and the βglobin locus control region (LCR) 27 would now be classified as super enhancers 28 .”
Biomolecular Condensates and Cancer
Boija, A., Klein, I. A., & Young, R. A. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.003 · Cited by 338
“Oncogene activation is often accomplished by the formation of super-enhancers, which are clusters of enhancers occupied by exceptionally high densities of transcriptional components that drive high-level expression of genes (Bradner et al., 2017; Hnisz et al., 2013; Lovén et al., 2013).”
BackgroundSelf-citationJunk DNA and the long non-coding RNA twist in cancer genetics
Ling, H. Y., Vincent, K., Pichler, M., Fodde, R., Berindan‐Neagoe, I., Slack, F. J., & Călin, G. A. (2015) · Oncogene · doi:10.1038/onc.2014.456 · Cited by 335
Establishment, maintenance, and recall of inflammatory memory
Larsen, S. B., Cowley, C. J., Sajjath, S. M., Barrows, D., Yang, Y., Carroll, T. S., & Fuchs, E. V. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.07.001 · Cited by 327
Epigenetic regulation of T cell exhaustion
Belk, J. A., Dániel, B., & Satpathy, A. T. (2022) · Nature Immunology · doi:10.1038/s41590-022-01224-z · Cited by 346
Cai, Y., Zhang, Y., Loh, Y. P., Tng, J. Q., Lim, M. C., Cao, Z., Raju, A., Lieberman Aiden, E., Li, S., Manikandan, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-20940-y · Cited by 321
Plastic roles of pericytes in the blood–retinal barrier
Park, D. Y., Lee, J., Kim, J., Kim, K., Hong, S., Han, S., Kubota, Y., Augustin, H. G., Ding, L., Kim, J. W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15296 · Cited by 336
Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease
Gilsbach, R., Preißl, S., Grüning, B. A., Schnick, T., Burger, L., Beneš, V., Würch, A., Bönisch, U., Günther, S., Backofen, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms6288 · Cited by 328
The once and future gene therapy
Bulaklak, K., & Gersbach, C. A. (2020) · Nature Communications · doi:10.1038/s41467-020-19505-2 · Cited by 343
Integrator mediates the biogenesis of enhancer RNAs
Lai, F., Gardini, A., Zhang, A., & Shiekhattar, R. (2015) · Nature · doi:10.1038/nature14906 · Cited by 331
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability
Gryder, B. E., Yohe, M. E., Chou, H.-C., Zhang, X., Marques, J. G., Wachtel, M., Schaefer, B. W., Sen, N., Song, Y., Gualtieri, A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1297 · Cited by 317
“Super Enhancer Analysis in RMS Cell Lines and Primary Tumors Implicates MYOD, MYOG, and MYCN as Master Regulators A small fraction of active enhancers acquire a large fraction of transcriptional machinery and active chromatin marks (frequently demarcated by H3K27ac), and have been defined as super enhancers (22, 23).”
A gene–environment-induced epigenetic program initiates tumorigenesis
Alonso‐Curbelo, D., Ho, Y.-J., Burdziak, C., Mååg, J. L. V., Morris, J. P., Chandwani, R., Chen, H.-A., Tsanov, K. M., Barriga, F. M., Luan, W., et al. (2021) · Nature · doi:10.1038/s41586-020-03147-x · Cited by 311
Cyclin-dependent protein kinases and cell cycle regulation in biology and disease
Pellarin, I., Dall’Acqua, A., Favero, A., Segatto, I., Rossi, V., Crestan, N., Karimbayli, J., Belletti, B., & Baldassarre, G. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02080-z · Cited by 381
Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis
Carrer, A., Trefely, S., Zhao, S., Campbell, S. L., Norgard, R. J., Schultz, K. C., Sidoli, S., Parris, J. L. D., Affronti, H. C., Sivanand, S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0567 · Cited by 313
“We also tested regulation of H3K27ac at the EGFR super-enhancer (35) using primers spanning the region (Supplementary Figure S6F).”
BackgroundMethodEnhancer 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
GRID-seq reveals the global RNA–chromatin interactome
Li, X., Zhou, B., Chen, L., Gou, L., Li, H., & Fu, X. (2017) · Nature Biotechnology · doi:10.1038/nbt.3968 · Cited by 304
CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance
Wang, C., Li, Y., Jia, L., Kim, J. K., Li, J., Deng, P., Zhang, W., Krebsbach, P. H., & Wang, C. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.04.011 · Cited by 314
A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples
Chen, H., Li, C., Peng, X., Zhou, Z., Weinstein, J. N., Johnson, R., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.027 · Cited by 300
“Despite recent systematic efforts, including genome-wide profiling of tissue and cell line collections (ENCODE Project Consortium, 2012; Hnisz et al., 2013; Roadmap Epigenomics Consortium et al., 2015) and a pan-cancer analysis of some super-enhancers (Zhang et al.”
BackgroundHosein, A. N., Huang, H., Wang, Z., Parmar, K., Du, W., Huang, J., Maitra, A., Olson, E., Verma, U., & Brekken, R. A. (2019) · JCI Insight · doi:10.1172/jci.insight.129212 · Cited by 302
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
Self-citationModels of human core transcriptional regulatory circuitriesPreprint
Saint‐André, V., Alexander Joel Federation, Lin, C. Y., Abraham, B. J., Reddy, J., Lee, T. I., Bradner, J. E., & Young, R. A. (2016) · Genome Research · doi:10.1101/gr.197590.115 · Cited by 303
“…key control information flows from a small number of core TFs. Recent studies have revealed that core TFs bind clusters of enhancers called super-enhancers and that the super-enhancer (SE)associated genes include those encoding the core TFs themselves (Hnisz et al. 2013, 2015; Whyte et al. 2013).”
BackgroundInfluentialSelf-citationDiscovery of stimulation-responsive immune enhancers with CRISPR activation
Simeonov, D. R., Gowen, B. G., Boontanrart, M., Roth, T. L., Gagnon, J. D., Mumbach, M. R., Satpathy, A. T., Lee, Y., Bray, N. L., Chan, A. Y., et al. (2017) · Nature · doi:10.1038/nature23875 · Cited by 297
Deciphering the multi-scale, quantitative cis-regulatory code
Kim, S., & Wysocka, J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.032 · Cited by 302
Genetics and Pathogenesis of Inflammatory Bowel Disease
Liu, T.-C., & Stappenbeck, T. S. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044152 · Cited by 289
“Super-enhancers are a group of transcriptional factors important for genes linked with cell identity and genetic risk of disease (49).”
BackgroundGerhäuser, C., Favero, F., Risch, T. S., Simon, R., Feuerbach, L., Assenov, Y., Heckmann, D., Sidiropoulos, N., Waszak, S. M., Hübschmann, D., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.10.016 · Cited by 296
p21 produces a bioactive secretome that places stressed cells under immunosurveillance
Sturmlechner, I., Zhang, C., Sine, C. C., van Deursen, E.-J., Jeganathan, K. B., Hamada, N., Grasic, J., Friedman, D., Stutchman, J. T., Can, I., et al. (2021) · Science · doi:10.1126/science.abb3420 · Cited by 295
“Superenhancers are large enhancers that are highly enriched in certain chromatin modifications and bind large amounts of numerous transcription factors (TFs) and coactivators (21, 22).”
BackgroundNakayama, R. T., Pulice, J. L., Valencia, A. M., McBride, M. J., McKenzie, Z. M., Gillespie, M. A. K., Ku, W. L., Teng, M., Cui, K., Williams, R. T., et al. (2017) · Nature Genetics · doi:10.1038/ng.3958 · Cited by 300
“g i BRG1 conserved target genes (10,896) H3K4me3-only (9,820) Bivalent (875) H3K27me3-only (23) Neither (178)”
BackgroundYAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers
Galli, G. G., Carrara, M., Yuan, W.-C., Valdes-Quezada, C., Gurung, B., Pepe-Mooney, B., Zhang, T., Geeven, G., Gray, N. S., de Laat, W., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.001 · Cited by 290
Boi, M., Gaudio, E., Bonetti, P., Kwee, I., Bernasconi, E., Tarantelli, C., Rinaldi, A., Testoni, M., Cascione, L., Ponzoni, M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1561 · Cited by 296
Dealing with Pervasive Transcription
Jensen, T. H., Jacquier, A., & Libri, D. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.10.032 · Cited by 306
Tracking the embryonic stem cell transition from ground state pluripotency
Kalkan, T., Olova, N. N., Roode, M., Mulas, C., Lee, H. J., Nett, I., Marks, H., Walker, R. V., Stunnenberg, H. G., Lilley, K. S., et al. (2017) · Development · doi:10.1242/dev.142711 · Cited by 295
“By contrast, ES cell ‘super enhancers’ (SEs) defined in serum-cultured ES cells (Whyte et al., 2013; Hnisz et al., 2013) exhibited low and relatively constant methylation levels in 2i, 16h and 25h-H cells, with a small increase in 25h-L cells but below the genome average (Fig.”
BackgroundLiu, C.-F., & Lefebvre, V. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv688 · Cited by 287
“The notion of SEs was recently introduced to designate very active enhancers or clusters of enhancers that are used as hubs by master transcription factors to govern the expression of major cell identity genes in embryonic stem cells and other cell types (31,32).”
BackgroundHierarchy within the mammary STAT5-driven Wap super-enhancer
Shin, H. Y., Willi, M., Yoo, K. H., Zeng, X., Wang, C., Metser, G., & Hennighausen, L. (2016) · Nature Genetics · doi:10.1038/ng.3606 · Cited by 282
“While 7% (32) of all super-enhancers were not occupied at p13 and were established only at day 1 of lactation (L1), some constituent enhancers within the remaining 93% (408) super-enhancers showed already limited TF occupancy at p13 (Fig.”
BackgroundOunzain, S., Micheletti, R., Arnan, C., Plaisance, I., Cecchi, D., Schroen, B. L. M., Reverter, F., Alexanian, M., Gonzales, C., Ng, S., et al. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.09.016 · Cited by 285
Super-Enhancer-Mediated RNA Processing Revealed by Integrative MicroRNA Network Analysis
Suzuki, H. I., Young, R. A., & Sharp, P. A. (2017) · Cell · doi:10.1016/j.cell.2017.02.015 · Cited by 284
“Computational methods for super-enhancer-associated miRNAs in human samples Super-enhancers and SE-miRNAs in human samples—Genomic coordinates of SEs and TEs in 86 human samples were downloaded from (Hnisz et al., 2013).”
InfluentialSelf-citationA cellular and molecular view of T helper 17 cell plasticity in autoimmunity
Stadhouders, R., Lubberts, E., & Hendriks, R. W. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.007 · Cited by 298
Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes
Zamudio, A. V., Dall’Agnese, A., Henninger, J. E., Manteiga, J. C., Afeyan, L. K., Hannett, N. M., Coffey, E. L., Li, C. H., Oksuz, O., Sabari, B. R., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.016 · Cited by 281
“Cancer cells develop genomic alterations that create super-enhancers at driver oncogenes (Chapuy et al., 2013; Hnisz et al., 2013; Lin et al., 2016; Mansour et al., 2014; Zhang et al., 2016), and these oncogenes are especially responsive to oncogenic signaling (Hnisz et al.”
BackgroundSelf-citationZhu, Y., Gujar, A. D., Wong, C., Tjong, H., Ngan, C. Y., Gong, L., Chen, Y., Kim, H., Liu, J., Li, M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.03.006 · Cited by 275
Methods for ChIP-seq analysis: A practical workflow and advanced applications
Nakato, R., & Sakata, T. (2021) · Methods · doi:10.1016/j.ymeth.2020.03.005 · Cited by 267
Durbin, A. D., Zimmerman, M. W., Dharia, N. V., Abraham, B. J., Iniguez, A. B., Weichert‐Leahey, N., He, S., Krill-Burger, J. M., Root, D. E., Vázquez, F., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0191-z · Cited by 279
Self-citationMiguel-Escalada, I., Bonàs‐Guarch, S., Cebola, I., Ponsa-Cobas, J., Mendieta-Esteban, J., Atla, G., Javierre, B. M., Rolando, D., Farabella, I., Morgan, C. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0457-0 · Cited by 269
Adipose tissue retains an epigenetic memory of obesity after weight loss
Hinte, L. C., Castellano‐Castillo, D., Ghosh, A., Melrose, K., Gasser, E., Noé, F., Massier, L., Dong, H., Sun, W., Hoffmann, A., et al. (2024) · Nature · doi:10.1038/s41586-024-08165-7 · Cited by 320
“Enhancers are key drivers of cellular identity and cell fate 51,52 .”
A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma
Chen, X., Zhang, M., Gan, H., Wang, H., Lee, J., Fang, D., Kitange, G. J., He, L., Hu, Z., Parney, I. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05373-4 · Cited by 270
Epigenetic Regulation of Pluripotency and Differentiation
Boland, M. J., Nazor, K. L., & Loring, J. F. (2014) · Circulation Research · doi:10.1161/circresaha.115.301517 · Cited by 284
Chen, Q., Yang, B.-H., Liu, X., Zhang, X. D., Zhang, L., & Liu, T. (2022) · Theranostics · doi:10.7150/thno.73223 · Cited by 285
Affer, M., Chesi, M., Chen, W. D., Keats, J. J., Demchenko, Y. N., Tamizhmani, K., Garbitt, V. M., Riggs, D. L., Brents, L. A., Roschke, A. V., et al. (2014) · Leukemia · doi:10.1038/leu.2014.70 · Cited by 273
Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs
Hadi, K., Yao, X., Behr, J. M., Deshpande, A. S., Xanthopoulakis, C., Tian, H., Kudman, S., Rosiene, J. A., Darmofal, M., DeRose, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.006 · Cited by 249
“Applying fishHook to find recurrent pyrgo hotspots across 8,642 nonoverlapping previously annotated superenhancer regions (Hnisz et al., 2013) (see STAR Methods), we found 16 loci were significantly mutated above background (false discovery rate [FDR] < 0.”
BackgroundYoo, S., Song, Y. S., Lee, E. K., Hwang, J., Kim, H. H., Jung, G., Kim, Y. A., Kim, S., Cho, S. W., Won, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10680-5 · Cited by 269
A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells
Diao, Y., Fang, R., Li, B., Meng, Z., Yu, J., Qiu, Y., Lin, K. C., Huang, H., Liu, T., Marina, R. J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4264 · Cited by 259
“S5C for other features), consistent with previous studies highlighting the role of clustered TF binding sites in gene regulation 25,29 .”
B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity
Qian, J., Wang, Q., Dose, M., Pruett, N. D., Kieffer-Kwon, K.-R., Resch, W., Liang, G., Tang, Z., Mathé, E. A., Benner, C. W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.013 · Cited by 279
Cho, J.-W., Hong, M. H., Ha, S., Kim, Y., Cho, B. C., Lee, I., & Kim, H. R. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00493-8 · Cited by 277
Targeting signaling pathways in prostate cancer: mechanisms and clinical trials
He, Y., Xu, W., Xiao, Y., Huang, H., Gu, D., & Ren, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01042-7 · Cited by 287
“Activation of histone acetyltransferases, such as p300 and CBP (CREB-binding protein), is highly associated with increased modification of H3K27ac.(419) Furthermore, p300 and CBP play crucial roles in regulating key genes in PCa, including AR target genes.”
BackgroundDuan, Q., McMahon, S., Anand, P., Shah, H., Thomas, S., Salunga, H. T., Huang, Y., Zhang, R., Sahadevan, A., Lemieux, M. E., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah5084 · Cited by 262
“Target gene specificity is achieved, in part, because the BRD4 coactivator protein is asymmetrically enriched at massive cell state–specific enhancers (or superenhancers) (26, 27).”
BackgroundThe Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis
Aldiri, I., Xu, B., Wang, L., Chen, X. '., Hiler, D. J., Griffiths, L. M., Valentine, M. B., Shirinifard, A., Thiagarajan, S., Sablauer, A., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.022 · Cited by 252
“Individual enhancers and large clusters of enhancers called super-enhancers activate individual genes within TADs by looping-out the intervening DNA (Hnisz et al., 2013).”
BackgroundMethodInfluentialGenetic architecture of subcortical brain structures in 38,851 individuals
Satizábal, C. L., Adams, H. H. H., Hibar, D. P., White, C. C., Knol, M. J., Stein, J. L., Scholz, M. R., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G. V., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0511-y · Cited by 267
“Similarly, strong enrichment was observed for regular enhancers (H3K27ac annotations from Hnisz et al. 31 ) in several subcortical structures, explaining over 60% of their SNP heritability.”
BackgroundSelf-citationEnhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation
Lee, J.-H., Wang, R., Xiong, F., Krakowiak, J., Liao, Z., Nguyen, P. T.-M., Moroz, E., Shao, J., Zhu, X., Bolt, M. J., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.024 · Cited by 281
NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers
Wang, H., Zang, C., Taing, L., Arnett, K. L., Wong, Y. J., Pear, W. S., Blacklow, S. C., Liu, X. S., & Aster, J. C. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315023111 · Cited by 252
Autoimmune diseases — connecting risk alleles with molecular traits of the immune system
Gutiérrez‐Arcelus, M., Rich, S. S., & Raychaudhuri, S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.33 · Cited by 256
The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia
Sánchez-Martín, M., & Ferrando, A. A. (2017) · Blood · doi:10.1182/blood-2016-09-692582 · Cited by 262
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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