The DOI matches its Crossref record; 160 of the 164 references it cites were found in a registry or an index.
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.
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 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]
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
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
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
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
Self-citation
Flagged first, then by citations
4 of the 164 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–500 of 1,018
Feng, W., Kawauchi, D., Körkel-Qu, H., Deng, H., Serger, E., Sieber, L., Lieberman, J. A., Jimeno-González, S., Lambo, S., Hanna, B. S., et al. (2017) · Nature Communications · doi:10.1038/ncomms14758 · Cited by 136
BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
Study, D. D. D., Olley, G., Ansari, M., Bengani, H., Grimes, G. R., Rhodes, J., von Kriegsheim, A., Blatnik, A., Stewart, F. J., Wakeling, E. L., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0042-y · Cited by 136
Biomolecular condensates as arbiters of biochemical reactions inside the nucleus
Laflamme, G., & Mekhail, K. (2020) · Communications Biology · doi:10.1038/s42003-020-01517-9 · Cited by 126
Genome-wide association study identifies multiple susceptibility loci for glioma
Kinnersley, B., Labussière, M., Holroyd, A., Stefano, A. L. D., Broderick, P., Vijayakrishnan, J., Mokhtari, K., Delattre, J., Gousias, K., Schramm, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms9559 · Cited by 133
Potent and selective bivalent inhibitors of BET bromodomains
Waring, M. J., Chen, H., Rabow, A. A., Walker, G. E., Bobby, R., Boiko, S., Bradbury, R. H., Callis, R. J., Clark, E. A., Dale, I. L., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2210 · Cited by 132
“3-Halotag (NM_002107) and either NanoLuc-BRD4 full-length (1-1362) (060885), NanoLuc-BRD4 full-length N433F mutant, or NanoLuc-N-terminal”
BackgroundMethodInfluentialThe roles and regulation of the KLF5 transcription factor in cancers
Luo, Y., & Chen, C. (2021) · Cancer Science · doi:10.1111/cas.14910 · Cited by 136
An encyclopedia of enhancer-gene regulatory interactions in the human genome
Gschwind, A. R., Mualim, K. S., Karbalayghareh, A., Sheth, M. U., Dey, K. K., Jagoda, E., Nurtdinov, R. N., Xi, W., Tan, A. S., Jones, H., et al. (2023) · doi:10.1101/2023.11.09.563812 · Cited by 119
The genetic regulatory signature of type 2 diabetes in human skeletal muscle
Scott, L. J., Erdos, M. R., Huyghe, J. R., Welch, R., Beck, A. T., Wolford, B. N., Chines, P. S., Didion, J. P., Narisu, N., Stringham, H. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11764 · Cited by 125
Smith, D. K., Yang, J., Liu, M.-L., & Zhang, C. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.09.013 · Cited by 131
“Lineage-determinative transcription factors can bind within localized regions of chromatin containing high densities of histone modifications such as H3K27 acetylation, known as super-enhancers, to regulate gene expression (Hnisz et al., 2013).”
BackgroundAmplifying gene expression with RNA-targeted therapeutics
Khorkova, O., Stahl, J., Joji, A., Volmar, C., & Wahlestedt, C. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00704-7 · Cited by 136
Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer
Zhang, H., Qi, J., Reyes, J. M., Li, L., Rao, P. K., Li, F., Lin, C. Y., Perry, J. A., Lawlor, M. A., Alexander Joel Federation, et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0164 · Cited by 133
“We constructed an SE-defined transcriptional network for normal and tumorigenic cell states by integrating maps of SE-associated master TFs with TF binding site data to reconstruct the core transcriptional regulatory circuitry (38).”
MethodCheung, K., Lu, G., Sharma, R., Vincek, A. S., Zhang, R., Plotnikov, A. N., Zhang, F., Zhang, Q., Ju, Y., Hu, Y., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615601114 · Cited by 132
“BET proteins play a multifaceted role in gene transcription through their tandem bromodomains binding to lysine-acetylated histones and transcription factors during chromatin opening, transcription factor recruitment to target gene promoter and enhancer sites, and activation of paused RNA polymerase II (PolII) transcr…”
BackgroundStructure and function of the Nppa–Nppb cluster locus during heart development and disease
Man, J. C. K., Barnett, P., & Christoffels, V. M. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2737-0 · Cited by 132
“Furthermore, this regulatory region is being described as a “super enhancer” [75, 76].”
Homeobox oncogene activation by pan-cancer DNA hypermethylation
Su, J., Huang, Y., Cui, X., Wang, X., Zhang, X., Lei, Y., Xu, J., Lin, X., Chen, K., Lv, J., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1492-3 · Cited by 130
“Also, a human genome-wide enhancer cluster was obtained from the ChIP-seq datasets of H3K27ac peaks in 88 human cell types [25].”
BackgroundMethodCharlet, J., Duymich, C. E., Lay, F. D., Mundbjerg, K., Dalsgaard Sørensen, K., Liang, G., & Jones, P. A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.033 · Cited by 128
“We then investigated the DNA methylation status of the normal human mammary epithelial cells (HMECs) and the breast cancer cell line MCF7 as well as normal prostate epithelial cells (PrECs) and the prostate cancer cells PC3 (Figures 1A– 1D).”
MethodInfluentialNguyen, V. T. M., Barozzi, I., Faronato, M., Lombardo, Y., Steel, J. H., Patel, N. R., Darbre, P. D., Castellano, L., Győrffy, B., Woodley, L., et al. (2015) · Nature Communications · doi:10.1038/ncomms10044 · Cited by 125
“Adapting a previously published approach 27 , we identified a set of 710 SEs with different types of distribution across ETR cells (Supplementary Fig.”
Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition
Chang, H., Liu, Y., Xue, M., Liu, H., Du, S., Zhang, L., & Wang, P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw126 · Cited by 126
“We applied the TPM cutoff to focus on the TFs with relatively high expression levels, an intrinsic characteristic of master TFs that provides advantages in competing for co-factors to dominate the transcriptional landscape (12).”
BackgroundMethodThe transcriptional regulator Aire binds to and activates super-enhancers
Bansal, K., Yoshida, H., Benoist, C. O., & Mathis, D. J. (2017) · Nature Immunology · doi:10.1038/ni.3675 · Cited by 127
“Super-enhancers are chromatin elements that serve as extended and overloaded depots for a multiplicity of general and cell-type-specific transcription factors 19,20 .”
Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia
Fabbri, G., Holmes, A. B., Viganotti, M., Scuoppo, C., Belver, L., Herranz, D., Yan, X., Kieso, Y., Rossi, D., Gaïdano, G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702564114 · Cited by 128
“NOTCH1 direct targets specifically relevant for the B-cell phenotype appear to be regulated via direct activation of the corresponding promoters, as well as via longrange interactions occurring at superenhancer sites, consistent with the role of these large regulatory elements in orchestrating the expression of cell-t…”
BackgroundZhang, X., Choi, P. S., Francis, J. M., Gao, G. F., Campbell, J. D., Ramachandran, A., Mitsuishi, Y., Ha, G., Shih, J., Vázquez, F., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0532 · Cited by 126
STAT3 Interactors as Potential Therapeutic Targets for Cancer Treatment
Laudisi, F., Cherubini, F., Monteleone, G., & Stolfi, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061787 · Cited by 133
“Notably, STAT3 was recently reported to be one of the key transcription factors involved in the formation of super-enhancers [35,36] and this further pinpoints the role of STAT3 interactome as an exceptionally interesting drug target.”
BackgroundBRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses
Dey, A., Yang, W., Gégonne, A., Nishiyama, A., Pan, R., Yagi, R., Grinberg, A., Finkelman, F. D., Pfeifer, K. E., Zhu, J., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100293 · Cited by 128
“SEs are large regulatory DNAs, enriched with RNA polymerase II (PoI II) and acetylated H3 at K27 (H3K27ac) (Hnisz et al , 2013).”
InfluentialRyan, R. J. H., Drier, Y., Whitton, H. J., Cotton, M. J., Kaur, J., Issner, R., Gillespie, S. M., Epstein, C. B., Nardi, V., Sohani, A. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0370 · Cited by 127
“Super-enhancer analysis of H3K27ac ChIP-Seq was performed with MACS and ROSE as described (28).”
MethodGriffon, A., Barbier, Q., Dalino, J., van Helden, J., Spicuglia, S., & Ballester, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1280 · Cited by 126
G-quadruplex DNA structures in human stem cells and differentiation
Zyner, K. G., Simeone, A., Flynn, S. M., Doyle, C., Marsico, G., Adhikari, S., Portella, G., Tannahill, D., & Balasubramanian, S. (2022) · Nature Communications · doi:10.1038/s41467-021-27719-1 · Cited by 124
Lin, D., Dinh, H. Q., Xie, J., Mayakonda, A., Silva, T. C., Jiang, Y., Ding, L., He, J., Xu, X., Hao, J., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-314607 · Cited by 119
“45 Importantly, H3K27ac modification was markedly diminished in OSCC cells in the same region that both gained DNA methylation (figure 6H, between red dotted lines) and correlated with ZFP36L2 silencing (figure 6F,G).”
Connections Between Metabolism and Epigenetics in Programming Cellular Differentiation
Chisolm, D. A., & Weinmann, A. S. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053127 · Cited by 133
Regulatory functions of the Mediator kinases CDK8 and CDK19
Fant, C. B., & Taatjes, D. J. (2018) · Transcription · doi:10.1080/21541264.2018.1556915 · Cited by 131
“The Mediator kinases CDK8 and CDK19 regulate TF function through phosphorylation [45,46]; in addition, Mediator appears to be required for expression of most, if not all, pol II transcripts in mammalian genomes, and ChIP-Seq experiments indicate that the CDK8 module co-localizes with Mediator genome-wide [2,3], includ…”
BackgroundTissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer
Teng, S., Li, Y. E., Yang, M., Qi, R., Huang, Y., Wang, Q., Zhang, Y., Chen, S., Li, S., Lin, K., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0259-z · Cited by 131
Nesterov, S. V., Ilyinsky, N. S., & Uversky, V. N. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119102 · Cited by 121
Lee, R., Kang, M.-K., Kim, Y.-J., Yang, B., Shim, H., Kim, S., Kim, K., Yang, C. M., Min, B.-G., Jung, W.-J., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1242 · Cited by 123
Novo, C. L., Javierre, B.-M., Cairns, J., Segonds-Pichon, A., Wingett, S. W., Freire-Pritchett, P., Furlan-Magaril, M., Schoenfelder, S., Fraser, P., & Rugg-Gunn, P. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.040 · Cited by 119
“A subset of enhancers, known as super-enhancers (SEs; Hnisz et al., 2013; Whyte et al., 2013) or stretch enhancers (Parker et al.”
BackgroundInfluentialBET inhibition disrupts transcription but retains enhancer-promoter contact
Crump, N. T., Ballabio, E., Godfrey, L., Thorne, R., Repapi, E., Kerry, J., Tapia, M., Hua, P., Lagerholm, C., Filippakopoulos, P., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20400-z · Cited by 123
Epigenetic Regulation of Monocyte and Macrophage Function
Hoeksema, M. A., & de Winther, M. P. J. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6695 · Cited by 128
Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis
Sandoval, G. J., Pulice, J. L., Pakula, H., Schenone, M., Takeda, D. Y., Pop, M. S., Boulay, G., Williamson, K. E., McBride, M. J., Pan, J., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.040 · Cited by 122
“As transcription factors and chromatin regulators exhibit varying degrees of similarity in genome-wide occupancy patterns (Hnisz et al., 2013), we sought to determine whether ERG has a direct, instructive role in dictating BAF complex localization.”
Miyagawa, K., Shi, M., Chen, P.-I., Hennigs, J. K., Zhao, Z., Wang, M., Li, C. G., Saito, T., Taylor, S., Sa, S., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.313374 · Cited by 121
Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration
Lim, Y. W., Chen‐Harris, H., Mayba, O., Lianoglou, S., Wüster, A., Bhangale, T., Khan, Z., Mariathasan, S., Daemen, A., Reeder, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804506115 · Cited by 120
“We performed our analyses using SNP-gene pair P values computed from bladder urothelial carcinoma (BLCA) and lung adenocarcinoma (LUAD), where enhancer annotations were available for the corresponding healthy tissue (21).”
MethodFerreira, M. A. R., Gamazon, E. R., Al‐Ejeh, F., Aittomäki, K., Andrulis, I. L., Anton‐Culver, H., Arason, A., Arndt, V., Aronson, K. J., Arun, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08053-5 · Cited by 127
BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells
Debruyne, D. N., Dries, R., Sengupta, S., Seruggia, D., Gao, Y., Sharma, B., Huang, H., Moreau, L. A., McLane, M., Day, D. S., et al. (2019) · Nature · doi:10.1038/s41586-019-1472-0 · Cited by 126
Self-citationAKIRIN2 controls the nuclear import of proteasomes in vertebrates
de Almeida, M., Hinterndorfer, M., Brunner, H. L., Grishkovskaya, I., Singh, K., Schleiffer, A., Jude, J., Deswal, S., Kalis, R., Vunjak, M., et al. (2021) · Nature · doi:10.1038/s41586-021-04035-8 · Cited by 123
Kalna, V., Yang, Y., Peghaire, C. R., Frudd, K., Hannah, R., Shah, A. V., Osuna Almagro, L., Boyle, J. J., Göttgens, B., Ferrer, J., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.313788 · Cited by 119
Caslini, C., Hong, S., Ban, Y. J., Chen, X. S., & Ince, T. A. (2019) · Oncogene · doi:10.1038/s41388-019-0897-0 · Cited by 121
A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer
Chen, H., & Liang, H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.020 · Cited by 125
“Cancer Cell 38, 1–15, November 9, 2020 11 regions: we collected 350 H3K27ac profiles from Cistrome (Liu et al., 2011) and SEdb (Jiang et al., 2019) and annotated the potential eRNA loci in an additional 350 Mb putative superenhancer.”
BackgroundInfluentialMarson, A., Housley, W. J., & Hafler, D. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78086 · Cited by 126
“Recent work suggests that this is a so-called “super-enhancer” locus, where a dense cluster of putative regulatory elements are active in T cells (71).”
BackgroundWu, T., Kamikawa, Y. F., & Donohoe, M. E. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.003 · Cited by 123
A microfluidic device for epigenomic profiling using 100 cells
Cao, Z., Chen, C., He, B., Tan, K., & Lu, C. (2015) · Nature Methods · doi:10.1038/nmeth.3488 · Cited by 111
Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome
Cohen, A. J., Saiakhova, A., Corradin, O., Luppino, J. M., Lovrenert, K., Bartels, C. F., Morrow, J. J., Mack, S. C., Dhillon, G. K., Beard, L., et al. (2017) · Nature Communications · doi:10.1038/ncomms14400 · Cited by 118
HACER: an atlas of human active enhancers to interpret regulatory variants
Wang, J., Dai, X., Berry, L. D., Cogan, J. D., Liu, Q., & Shyr, Y. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky864 · Cited by 110
“If we limit enhancers and enhancer-promoter interactions to HCT-116, a colon cancer cell line, we find seven enhancers upstream of the MYC gene (Supplementary Figure S4B); the first four and the last of these previously have been labelled as super-enhancers in HCT-116 (54,69).”
BackgroundThe role of photodynamic therapy on multidrug resistant breast cancer
Aniogo, E. C., George, B. P. A., & Abrahamse, H. (2019) · Cancer Cell International · doi:10.1186/s12935-019-0815-0 · Cited by 122
Single-Cell Epigenomics and Functional Fine-Mapping of Atherosclerosis GWAS Loci
Örd, T., Õunap, K., Stolze, L. K., Aherrahrou, R., Nurminen, V., Toropainen, A., Selvarajan, I., Lönnberg, T., Aavik, E., Ylä‐Herttuala, S., et al. (2021) · Circulation Research · doi:10.1161/circresaha.121.318971 · Cited by 112
RNA polymerase II dynamics shape enhancer–promoter interactions
Barshad, G., Lewis, J. J., Chivu, A. G., Abuhashem, A., Krietenstein, N., Rice, E. J., Ma, Y., Wang, Z., Rando, O. J., Hadjantonakis, A., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01442-7 · Cited by 123
Strategies to therapeutically modulate cytokine action
Leonard, W. J., & Lin, J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00746-x · Cited by 123
Multi-omic profiling of the developing human cerebral cortex at the single-cell level
Zhu, K., Bendl, J. M., Rahman, S., Vicari, J. M., Coleman, C., Clarence, T., Latouche, O., Tsankova, N. M., Li, A., Brennand, K., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg3754 · Cited by 117
“In previous studies, it has been shown that DORCs are often associated with super-enhancers — large clusters of enhancer regions that are known to play key regulatory roles in defining cell identity and are affected across multiple diseases ( 29 , 30 ).”
Enhancer methylation dynamics contribute to cancer plasticity and patient mortalityPreprint
Bell, R. E., Golan, T., Sheinboim, D., Malcov, H., Amar, D., Salamon, A., Liron, T., Gelfman, S., Gabet, Y., Ron Shamir, A., et al. (2016) · Genome Research · doi:10.1101/gr.197194.115 · Cited by 121
“ing expression programs (Hnisz et al. 2013) and are characterized”
Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia
Zeidner, J. F., & Karp, J. E. (2015) · Leukemia Research · doi:10.1016/j.leukres.2015.10.010 · Cited by 121
CDK7 Inhibition Suppresses Castration-Resistant Prostate Cancer through MED1 Inactivation
Rasool, R. U., Natesan, R., Deng, Q., Aras, S., Lal, P., Effron, S. S., Mitchell-Velasquez, E., Posimo, J. M., Carskadon, S. L., Baca, S. C., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0189 · Cited by 118
Nested epistasis enhancer networks for robust genome regulation
Lin, X., Liu, Y., Liu, S., Zhu, X., Wu, L., Zhu, Y., Zhao, D., Xu, X., Chemparathy, A., Wang, H., et al. (2022) · Science · doi:10.1126/science.abk3512 · Cited by 112
A simple method for generating high-resolution maps of genome-wide protein binding
Skene, P. J., & Henikoff, S. (2015) · eLife · doi:10.7554/elife.09225 · Cited by 117
“High resolution is especially a requirement at closely spaced transcription factor binding sites, such as locus control regions and super-enhancers, which have been shown to be vital to cell fate decisions and human diseases (Hnisz et al., 2013; Pott and Lieb, 2014).”
BackgroundMediator kinase module and human tumorigenesis
Clark, A. D., Oldenbroek, M., & Boyer, T. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1064854 · Cited by 121
“…is required for super-enhancer activity and also promotes physical and functional communion between regulator-bound enhancers and the basal transcriptional apparatus on core promoters (Hnisz et al., 2013; Kagey et al., 2010; Muto et al., 2014; Phillips-Cremins et al., 2013; Whyte et al., 2013).”
In the loop: promoter–enhancer interactions and bioinformatics
Mora, A., Sandve, G. K., Gabrielsen, O. S., & Eskeland, R. (2015) · Briefings in Bioinformatics · doi:10.1093/bib/bbv097 · Cited by 126
“group of putative strong enhancers spanning from a few kb to 50 kb, termed ‘super-enhancers’ [120, 164].”
BackgroundEmbryonic transcription is controlled by maternally defined chromatin state
Hontelez, S., van Kruijsbergen, I., Γεωργίου, Γ., van Heeringen, S. J., Bogdanović, O., Lister, R., & Veenstra, G. J. C. (2015) · Nature Communications · doi:10.1038/ncomms10148 · Cited by 117
“Large enhancer clusters (ECs) are thought to improve the stability of enhancer–promoter interactions, are associated with genes coding for developmental regulators, and have been implicated in cell differentiation 42–44 .”
Wang, X., Tucker, N. R., Rizki, G., Mills, R. W., Krijger, P. H. L., de Wit, E., Subramanian, V., Bartell, E., Nguyen, X.-X., Ye, J., et al. (2016) · eLife · doi:10.7554/elife.10557 · Cited by 114
“Previous studies have compared the number of GWAS SNPs overlapping a feature against the number expected for a randomly chosen region of similar size ( Maurano et al., 2012 ; Hnisz et al., 2013 ).”
Jiao, W., Chen, Y., Song, H., Li, D., Mei, H., Yang, F., Fang, E., Wang, X., Huang, K., Zheng, L., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0128-0 · Cited by 117
Evidence for additive and synergistic action of mammalian enhancers during cell fate determination
Choi, J., Lysakovskaia, K., Stik, G., Demel, C., Söding, J., Tian, T. V., Graf, T., & Cramer, P. (2021) · eLife · doi:10.7554/elife.65381 · Cited by 117
Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers
Li, Q., Lin, X., Yu, Y., Chen, L., Hu, Q., Chen, M., Cao, N., Zhao, C., Wang, C.-Y., Huang, C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26600-5 · Cited by 117
7SK-BAF axis controls pervasive transcription at enhancers
Flynn, R. A., Do, B. T., Rubin, A. J., Calo, E., Lee, B., Kuchelmeister, H. Y., Rale, M. J., Chu, C., Kool, E. T., Wysocka, J., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3176 · Cited by 113
IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression
Hipp, N., Symington, H. L., Pastoret, C., Caron, G., Monvoisin, C., Tarte, K., Fest, T., & Delaloy, C. (2017) · Nature Communications · doi:10.1038/s41467-017-01475-7 · Cited by 120
Into the Wild: GWAS Exploration of Non-coding RNAs
Giral, H., Landmesser, U., & Kratzer, A. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00181 · Cited by 113
“, in trans location to the variant), may help unravel the complex regulatory events of cardiovascular disease including underlying importance of enhancers or super-enhancers (88).”
BackgroundProtein phase separation and its role in tumorigenesis
Jiang, S., Fagman, J. B., Chen, C., Alberti, S., & Liu, B. (2020) · eLife · doi:10.7554/elife.60264 · Cited by 119
“For example, super-enhancers, which are clusters of several hundred enhancers, are bound cooperatively by transcription factors to drive robust transcription of genes for defining cell identity (Hnisz et al., 2013).”
BackgroundAPOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer
Periyasamy, M., Patel, H., Lai, C., Nguyen, V. T. M., Nevedomskaya, E., Harrod, A., Russell, R., Reményi, J., Ochocka, A. M., Thomas, R. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.066 · Cited by 110
“This was confirmed by strong enrichment for BRD4 and p300, two ubiquitous co-activators found at active regulatory elements (Hnisz et al., 2013).”
BackgroundJohnson, K. C., Houseman, E. A., King, J. E., von Herrmann, K. M., Fadul, C. E., & Christensen, B. C. (2016) · Nature Communications · doi:10.1038/ncomms13177 · Cited by 123
Yan, W., Chen, D., Schumacher, J., Durantini, D., Engelhorn, J., Chen, M., Carles, C. C., & Kaufmann, K. (2019) · Nature Communications · doi:10.1038/s41467-019-09513-2 · Cited by 116
Transcriptional Regulation by (Super)Enhancers: From Discovery to Mechanisms
Grosveld, F., van Staalduinen, J., & Stadhouders, R. (2021) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-122220-093818 · Cited by 115
From trans to cis: transcriptional regulatory networks in neocortical development
Shibata, M., Gulden, F. O., & Sestan, N. (2015) · Trends in Genetics · doi:10.1016/j.tig.2014.12.004 · Cited by 109
Enhanced Identification of Transcriptional Enhancers Provides Mechanistic Insights into Diseases
Murakawa, Y., Yoshihara, M., Kawaji, H., Nishikawa, M., Zayed, H., Suzuki, H., & Hayashizaki, Y. (2016) · Trends in Genetics · doi:10.1016/j.tig.2015.11.004 · Cited by 112
Nuclear receptors in cancer — uncovering new and evolving roles through genomic analysis
Dhiman, V. K., Bolt, M. J., & White, K. P. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.102 · Cited by 117
Scholz, B. A., Sumida, N., de Lima, C. D. M., Chachoua, I., Martino, M., Tzelepis, I., Nikoshkov, A., Zhao, H., Mehmood, R., Sifakis, E. G., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0535-3 · Cited by 114
DNA methylation dynamics in cellular commitment and differentiation
Suelves, M., Carrió, E., Núñez‐Álvarez, Y., & Peinado, M. A. (2016) · Briefings in Functional Genomics · doi:10.1093/bfgp/elw017 · Cited by 120
Non-coding RNAs, epigenetics, and cancer: tying it all together
Ferreira, H. J., & Esteller, M. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-017-9715-8 · Cited by 116
Domenico, A. D., Pipinikas, C., Maire, R., Bräutigam, K., Simillion, C., Dettmer, M. S., Vassella, E., Thirlwell, C., Perren, A. A., & Marinoni, I. (2020) · Communications Biology · doi:10.1038/s42003-020-01479-y · Cited by 115
GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
Styrkársdóttir, U., Stefánsson, Ó. A., Gunnarsdóttir, K., Þorleifsson, G., Lund, S. H., Stefánsdóttir, L., Juliusson, K., Agustsdottir, A. B., Zink, F., Halldorsson, G. H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09860-0 · Cited by 105
Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
Jia, Y., Chng, W. J., & Zhou, J. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0757-y · Cited by 120
TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers
Charlton, J., Jung, E. J., Mattei, A. L., Bailly, N., Liao, J., Martin, E. J., Gießelmann, P., Brändl, B., Stamenova, E. K., Müller, F.-J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0639-9 · Cited by 111
“For comparison to genomic features, BedTools was used to intersect methylation data within CpG islands 63 , coding features (RefSeq), H1 ESC-defined typical and super enhancers 32 and repeats (RepeatMasker).”
InfluentialRNA and liquid-liquid phase separation
Guo, Q., Shi, X., & Wang, X. (2021) · Non-coding RNA Research · doi:10.1016/j.ncrna.2021.04.003 · Cited by 121
Multhaup, M., Seldin, M. M., Jaffe, A. E., Lei, X., Kirchner, H., Mondal, P., Li, Y., Rodriguez, V., Drong, A., Hussain, M. A., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.014 · Cited by 112
Enhancer deregulation in cancer and other diseases
Herz, H. (2016) · BioEssays · doi:10.1002/bies.201600106 · Cited by 110
“BRD4 has a strong preference to bind to enhancers of oncogenic and lineage-specific genes also known as super enhancers (see above) making it a promising target [84, 85].”
BackgroundInfluentialWyss, A. B., Sofer, T., Lee, M. K., Terzikhan, N., Nguyen, J. N., Lahousse, L., Latourelle, J. C., Smith, A. V., Bartz, T. M., Feitosa, M. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05369-0 · Cited by 111
SEdb 2.0: a comprehensive super-enhancer database of human and mouse
Wang, Y., Song, C., Zhao, J., Zhang, Y., Zhao, X., Feng, C., Zhang, G., Zhu, J., Wang, F., Qian, F., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac968 · Cited by 111
Robson, M. I., de las Heras, J. I., Czapiewski, R., Sivakumar, A., Kerr, A. R. W., & Schirmer, E. C. (2017) · Genome Research · doi:10.1101/gr.212308.116 · Cited by 107
“To test this, a list of enhancer clusters/super-enhanc-ers identified as functioning during human T-cell activation by H3K27ac accumulation (Hnisz et al. 2013) were compared to Jurkat activation LADs.”
BackgroundPugacheva, E. M., Rivero-Hinojosa, S., Espinoza, C. A., Méndez-Catalá, C. F., Kang, S., Suzuki, T., Kosaka-Suzuki, N., Robinson, S., Nagarajan, V., Ye, Z., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0736-8 · Cited by 110
“The list of super enhancers (742) was adopted from [41].”
BackgroundMethodRecent developments in epigenetics of acute and chronic kidney diseases
Reddy, M. A., & Natarajan, R. D. (2015) · Kidney International · doi:10.1038/ki.2015.148 · Cited by 115
Suzuki, A., Makinoshima, H., Wakaguri, H., Esumi, H., Sugano, S., Kohno, T., Tsuchihara, K., & Suzuki, Y. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku885 · Cited by 109
The Role of STAT Signaling Pathways in the Pathogenesis of Systemic Lupus Erythematosus
Goropevšek, A., Holcar, M., & Avčin, T. (2016) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-016-8550-y · Cited by 113
“enriched in B and T helper cell enhancer clusters or superenhancers (SEs) [9, 10].”
BackgroundShared heritability and functional enrichment across six solid cancers
Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08054-4 · Cited by 110
Long non-coding RNAs: An emerging powerhouse in the battle between life and death of tumor cells
Xiong, X.-D., Ren, X., Cai, M., Yang, J. W., Liu, X., & Yang, J. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.04.001 · Cited by 109
Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration
Lucic, B., Chen, H., Kuzman, M., Zorita, E. V., Wegner, J., Minneker, V., Wang, W., Fronza, R., Laufs, S., Schmidt, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12046-3 · Cited by 111
Lee, K.-W., Yeo, S.-Y., Gong, J.-R., Koo, O.-J., Sohn, I., Lee, W. Y., Kim, H. C., Yun, S. H., Cho, Y. B., Choi, M.-A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30484-4 · Cited by 103
Zic2 Is an Enhancer-Binding Factor Required for Embryonic Stem Cell Specification
Luo, Z., Gao, X., Lin, C., Smith, E. R., Marshall, S. A., Swanson, S. K., Florens, L. A., Washburn, M. P., & Shilatifard, A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.007 · Cited by 110
Predicting chromatin organization using histone marks
Huang, J., Marco, E., Pinello, L., & Yuan, G. (2015) · Genome biology · doi:10.1186/s13059-015-0740-z · Cited by 116
“We also compared the hub locations with super-enhancers, which were previously shown to play an important role in the control of cell identity and diseases [19], and observed a 5-fold enrichment comparing to the genomic background.”
BackgroundInhibitors of bromodomain and extra‐terminal proteins for treating multiple human diseases
Kulikowski, E., Rakai, B. D., & Wong, N. C. W. (2020) · Medicinal Research Reviews · doi:10.1002/med.21730 · Cited by 109
“This developmental differentiation process involves a coordinated program requiring abundant expression of a well‐defined, but limited panel of genes, including lineage‐determining genes octamer‐binding transcription factor 4 (OCT4), sex determining region Y‐box transcription factor 2 (SOX2) and homeobox protein NANOG…”
BackgroundInfluential
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
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
