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 901–1,000 of 1,018
Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity
Bywater, M. J., Burkhart, D. L., Straube, J., Sabò, A., Pendino, V., Hudson, J. E., Quaife-Ryan, G. A., Porrello, E. R., Rae, J., Parton, R. G., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15552-x · Cited by 57
A first exon termination checkpoint preferentially suppresses extragenic transcription
Austenaa, L. M. I., Piccolo, V., Russo, M., Prosperini, E., Polletti, S., Polizzese, D., Ghisletti, S., Barozzi, I., Diaferia, G. R., & Natoli, G. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00572-y · Cited by 56
Yang, L.-X., Qi, C., Lu, S., Ye, X.-S., Merikhian, P., Zhang, D.-Y., Yao, T., Zhao, J.-S., Wu, Y., Jia, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55738-1 · Cited by 57
Missing heritability in Parkinson’s disease: the emerging role of non-coding genetic variation
Ohnmacht, J., May, P., Sinkkonen, L., & Krüger, R. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02184-0 · Cited by 60
“2012), in particular in regions controlling genes expressed and playing important roles in a cell typespecific manner (Hnisz et al. 2013).”
BackgroundMarques, J. G., Gryder, B. E., Pavlovic, B., Chung, Y., Ngo, Q. A., Frommelt, F., Gstaiger, M., Song, Y., Benischke, K., Laubscher, D., et al. (2020) · eLife · doi:10.7554/elife.54993 · Cited by 59
“During normal development, SEs regulate cell identity while in cancer they drive high expression of oncogenes (Hnisz et al., 2013; Sengupta and George, 2017).”
BackgroundRenin Cells, the Kidney, and Hypertension
Sequeira-Lopez, M. L. S., & Gomez, R. A. (2021) · Circulation Research · doi:10.1161/circresaha.121.318064 · Cited by 58
HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock
Himanen, S. V., Puustinen, M. C., Silva, A. J. D., Vihervaara, A., & Sistonen, L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac493 · Cited by 57
“Intriguingly, the profiles of downregulated enhancers, showed several Pol II peaks, which implies that transcriptionally active enhancer clusters, also known as super-enhancers (45), lose engaged Pol II under stress conditions.”
Marchal, C., Singh, N., Batz, Z. A., Advani, J., Jaeger, C., Corso‐Díaz, X., & Swaroop, A. (2022) · Nature Communications · doi:10.1038/s41467-022-33427-1 · Cited by 54
The roles of Mediator complex in cardiovascular diseases
Schiano, C., Casamassimi, A., Vietri, M. T., Rienzo, M., & Claudio Napoli, A. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.04.012 · Cited by 59
Jiang, J. (2015) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2015.01.005 · Cited by 57
Hayashi, M., Jin, Y., Yorgov, D., Santorico, S. A., Hagman, J. R., Ferrara, T. M., Jones, K. L., Cavalli, G., Dinarello, C. A., & Spritz, R. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525001113 · Cited by 56
“Alternatively, bidirectional promoters often serve specialized functions (25), and it may be that the in vivo biological function of the HLA-A downstream regulatory region is more complex, perhaps acting as a superenhancer (26), locus control region (27), or other higher-order transcriptional regulatory element in the…”
BackgroundYoshida, J., Akagi, K., Misawa, R., Kokubu, C., Takeda, J., & Horie, K. (2017) · Scientific Reports · doi:10.1038/srep43613 · Cited by 62
Martínez, M. F. R., Medrano, S., Brown, R. I., Tufan, T., Shang, S., Bertoncello, N., Guessoum, O., Adli, M., Belyea, B., Sequeira-Lόpez, M. L. S., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci121361 · Cited by 54
“Renin cells possess a unique group of super-enhancers that differentiate them from other cell types Unlike typical enhancers, which are characterized by sharp and narrow (2-5 kb) peaks of histone H3 Lysine 27 acetylation (H3K27ac), super-enhancers contain larger domains of H3K27ac (20, 21) and are densely loaded with…”
Chen, Y., Xu, L., Mayakonda, A., Huang, M.-L., Kanojia, D., Tan, T. Z., Dakle, P., Lin, R. Y., Ke, X., SAID, J. W., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09257-z · Cited by 58
Integrated Pan-Cancer Map of EBV-Associated Neoplasms Reveals Functional Host–Virus Interactions
Chakravorty, S., Yan, B., Wang, C., Wang, L., Quaid, J. T., Lin, C. F., Briggs, S. D., Majumder, J., Canaria, D. A., Chauss, D., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0615 · Cited by 57
Li, Y., Gao, J., Kamran, M. Z., Harmacek, L. D., Danhorn, T., Leach, S. M., O’Connor, B. P., Hagman, J. R., & Huang, H. (2021) · Nature Communications · doi:10.1038/s41467-020-20766-0 · Cited by 56
Frazer, C., Staples, M. I., Kim, Y., Hirakawa, M., Dowell, M. A., Johnson, N. V., Hernday, A. D., Ryan, V. H., Fawzi, N. L., Finkelstein, I. J., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0760-7 · Cited by 56
“Close parallels with mammalian TRNs are also noted where high concentrations of TFs and cofactors can assemble at ‘super-enhancers’, and where these elements are integral to the control of cell identity 3,9,11,14,63 .”
The many faces of long noncoding RNA s
Gardini, A., & Shiekhattar, R. (2014) · FEBS Journal · doi:10.1111/febs.13101 · Cited by 58
Dynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte Differentiation
Cavazza, A., Miccio, A., Romano, O., Petiti, L., Tagliazucchi, G. M., Peano, C., Severgnini, M., Rizzi, E., Bellis, G. D., Bicciato, S., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.03.003 · Cited by 58
“Acetylation of H3K27 defines transcriptionally active enhancers and large clusters of enhancers (super-enhancers [SEs]) involved in the definition of cell and tissue identity (Hnisz et al., 2013).”
BackgroundHorie, M., Miyashita, N., Mikami, Y., Noguchi, S. F., Yamauchi, Y., Suzukawa, M., Fukami, T., Ohta, K., Asano, Y., Sato, S., et al. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00193.2017 · Cited by 55
The promise of enhancer-associated long noncoding RNAs in cardiac regeneration
Ounzain, S., & Pedrazzini, T. (2015) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2015.01.014 · Cited by 58
“[41] Hnisz D, Abraham BJ, Lee TI, et al.”
BackgroundInfluentialEpigenetic determinants of metastasis
Patel, S. A., & Vanharanta, S. (2016) · Molecular Oncology · doi:10.1016/j.molonc.2016.09.008 · Cited by 58
“Different tissues, including cancers, are thus characterized by unique gene expression profiles and chromatin landscapes (Hnisz et al., 2013).”
BackgroundKlein, R. H., Lin, Z., Hopkin, A. S., Gordon, W., Tsoi, L. C., Liang, Y., Gudjonsson, J. E., & D, B. A. M. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006745 · Cited by 54
“We also defined SEs using the H3K27ac mark [4, 6], identifying 783, 761, and 363 SEs in NHEK-P, NHEK-D, and NHEK-M, respectively (Fig 1A).”
BackgroundMethodInfluentialNew Insights into Lymphoma Pathogenesis
Elenitoba‐Johnson, K. S. J., & Lim, M. S. (2017) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043803 · Cited by 55
Niskanen, H., Tuszyńska, I., Zaborowski, R., Heinäniemi, M., Ylä‐Herttuala, S., Wilczyński, B., & Kaikkonen, M. U. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1214 · Cited by 63
“These two groups of DNA-bound factors have been previously shown to establish super-enhancers often found at genes that define cell identity (27).”
BackgroundMethodShaping Gene Expression by Landscaping Chromatin Architecture: Lessons from a Master
Sartorelli, V., & Puri, P. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.04.025 · Cited by 59
Tsuchiya, H., Ota, M., Sumitomo, S., Ishigaki, K., Suzuki, A., Sakata, T., Tsuchida, Y., Inui, H., Hirose, J., Kochi, Y., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2020-218189 · Cited by 58
S100A8/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation
Song, R., & Struhl, K. (2021) · Science Advances · doi:10.1126/sciadv.abe5357 · Cited by 55
Mikami, Y., Philips, R. L., Sciumè, G., Petermann, F., Meylan, F., Nagashima, H., Yao, C., Davis, F. P., Brooks, S. R., Sun, H., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.02.015 · Cited by 59
ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer
Pozo, K., Kollipara, R. K., Kelenis, D. P., Rodarte, K. E., Ullrich, M. S., Zhang, X., Minna, J. D., & Johnson, J. E. B. (2021) · iScience · doi:10.1016/j.isci.2021.102953 · Cited by 58
Paiva, I., Cellai, L., Mériaux, C., Poncelet, L., Nebie, O., Saliou, J., Lacoste, A., Papegaey, A., Drobecq, H., Gras, S. L., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci149371 · Cited by 60
“Histone H3 acetylation at lysine 27 (H3K27ac) is preferentially enriched at active enhancers (21), also forming large clusters of H3K27ac-enriched enhancers known as super-enhancers on highly transcribed genes that are cell- or tissue-specific (22, 23).”
BackgroundAn RNA-centric view of transcription and genome organization
Henninger, J. E., & Young, R. A. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.021 · Cited by 58
Self-citationPan-Cancer Analyses of the Nuclear Receptor Superfamily
Long, M. D., & Campbell, M. J. (2015) · Nuclear Receptor Research · doi:10.11131/2015/101182 · Cited by 56
Wang, E., Kawaoka, S., Roe, J.-S., Shi, J., Hohmann, A. F., Xu, Y., Bhagwat, A. S., Suzuki, Y., Kinney, J. B., & Vakoc, C. R. (2015) · eLife · doi:10.7554/elife.06377 · Cited by 54
“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 superenhancers that exhibit high levels of all regulators (Figure 3—figure supplement 1) (Hnisz et al., 2013).”
BackgroundEMBRACE, O. B. O., Zeng, C., Collaborators, B. O. G. S., HEBON, O. B. O., KConFab, O. B. O., AOCS Investigators, Guo, X., Long, J., Kuchenbaecker, K. B., Droit, A., et al. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0718-0 · Cited by 59
Wen, S., He, Y., Wang, L., Zhang, J., Quan, C., Niu, Y., & Huang, H. (2020) · Oncogene · doi:10.1038/s41388-020-01456-z · Cited by 55
Long Noncoding RNAs in Lung Cancer
Roth, A., & Diederichs, S. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_444 · Cited by 53
NF-κB–Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis
Rodrigues, P., Patel, S. A., Harewood, L., Olan, I., Vojtasova, E., Syafruddin, S. E., Zaini, M. N., Richardson, E. K., Burge, J., Warren, A. Y., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1211 · Cited by 56
“Enhancer activation landscapes are highly tissue specific, implying that enhancers and enhancer clusters are critical determinants of cell fate and identity (27,28).”
Nuclear Periphery Takes Center Stage: The Role of Nuclear Pore Complexes in Cell Identity and Aging
Cho, U. H., & Hetzer, M. W. (2020) · Neuron · doi:10.1016/j.neuron.2020.05.031 · Cited by 54
“Given that SEs regulate genes that determine cell fate (Hnisz et al., 2013), Nup93 can be considered a structural platform for cell identity maintenance and change.”
BackgroundMeng, H., & Bartholomew, B. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.813485 · Cited by 59
“enhancers in large domains, which often show high levels of RNAPII occupancy and are highly transcribed (87-89).”
BackgroundNeurogenetic disorders across the lifespan: from aberrant development to degeneration
Hickman, R. A., O’Shea, S. A., Mehler, M. F., & Chung, W. K. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00595-5 · Cited by 59
A framework for fibrolamellar carcinoma research and clinical trials
Dinh, T. A., Utria, A. F., Barry, K. C., Ma, R. K., Abou‐Alfa, G. K., Gordan, J. D., Jaffee, E. M., Scott, J. D., Zucman‐Rossi, J., O'Neill, A. F., et al. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00580-3 · Cited by 54
BRD4: a general regulator of transcription elongation
Altendorfer, E., Mochalova, Y., & Mayer, A. (2022) · Transcription · doi:10.1080/21541264.2022.2108302 · Cited by 59
“Super-enhancers are clusters of enhancers, which are occupied by a high density of transcription factors and components of the Pol II transcription machinery including BRD4 and Mediator, mainly controlling cell identity genes [100,101].”
BackgroundQiu, H., Makarov, V., Bolzenius, J. K., Halstead, A. M., Parker, Y., Wang, A., Iyer, G., Wise, H. C., Kim, D., Thayaparan, V., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-1444 · Cited by 52
“H3K27ac signals were stitched and ranked to identify superenhancers, which have been reported to control key aspects of cell identity and cancer biology (39).”
BackgroundEnhancer RNAs: mechanisms in transcriptional regulation and functions in diseases
Li, Q., Liu, X., Wen, J., Chen, X., Xie, B., & Zhao, Y. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01206-0 · Cited by 55
“Like typical enhancers, super enhancers can also be transcribed to form eRNAs, ChIP-Seq results suggested that super-enhancer regions were enriched with more RNA transcription signals than typical enhancer regions, which drove higher levels of target gene expression [46].”
BackgroundTead1 regulates the expression of Peripheral Myelin Protein 22 during Schwann cell development
Lopez‐Anido, C., Poitelon, Y., Gopinath, C., Moran, J. J. M., Ma, K. H., Law, W., Antonellis, A., Feltri, M. L., & Svaren, J. P. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw158 · Cited by 54
“Superenhancers regulate the expression of genes that drive cell identity (65), and exhibit cell lineage- and tissue-specificity (63,66).”
BackgroundTo Wnt or Lose: The Missing Non-Coding Linc in Colorectal Cancer
Shen, P., Pichler, M., Chen, M., Călin, G. A., & Ling, H. Y. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18092003 · Cited by 54
“(iii) DNA elements in this region have various enhancer activities that are affected by SNPs [43,44], and more recently this region was proposed as a typical example of a super-enhancer [45].”
BackgroundMediator Kinase Phosphorylation of STAT1 S727 Promotes Growth of Neoplasms With JAK-STAT Activation
Niţulescu, I., Meyer, S. C., Wen, Q. J., Crispino, J. D., Lemieux, M. E., Levine, R. L., Pelish, H. E., & Shair, M. D. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.11.013 · Cited by 55
“Super-enhancers (SEs) are large stretches of regulatory DNA loaded with transcriptional regulators that drive high expression of cell identity and disease genes (Hnisz et al., 2013; Lovén et al., 2013).”
BackgroundWeiss, R. B., Vieland, V. J., Dunn, D. M., Kaminoh, Y., Flanigan, K. M., & for the United Dystrophinopathy Project (2018) · Annals of Neurology · doi:10.1002/ana.25283 · Cited by 55
“Sample-level genotype data for GSE81046 were provided by Dr. Luis B. Barreiro, CHU Sainte-Justine/University of Montreal.28 UCSC genome browser BED Files of enhancers from human skeletal muscle myotubes were retrieved from Data S2 zipped file from Hinsz et al.29 Additional chromatin analysis tracks that were retrieved…”
MethodSuper-enhancers are transcriptionally more active and cell type-specific than stretch enhancers
Khan, A., Mathelier, A., & Zhang, X. (2018) · Epigenetics · doi:10.1080/15592294.2018.1514231 · Cited by 58
“Genes were assigned to super-enhancers and stretch enhancers based on proximity as descried in [16,17].”
BackgroundMethodCancer Stem Cells and Neuroblastoma: Characteristics and Therapeutic Targeting Options
Veschi, V., Verona, F., & Thiele, C. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00782 · Cited by 54
Huang, C., You, X., Dai, C., Xu, Q., Li, F., Wang, L., Huang, X., Wang, J., Li, S., Gao, Z., et al. (2020) · Advanced Science · doi:10.1002/advs.201902926 · Cited by 53
Higashijima, Y., Matsui, Y., Shimamura, T., Nakaki, R., Nagai, N., Tsutsumi, S., Abe, Y., Link, V. M., Osaka, M., Yoshida, M., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019103949 · Cited by 56
“Other studies demonstrated the importance of super enhancers (SEs), also known as stretch or large enhancer clusters, for the regulation of genes correlated with cell identity (Hnisz et al , 2013; Parker et al , 2013; Whyte et al , 2013; Suzuki et al , 2017).”
Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity
Shim, W. J., Sinniah, E., Xu, J., Vitrinel, B., Alexanian, M., Andreoletti, G., Shen, S., Sun, Y., Balderson, B., Boix, C. A., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.11.001 · Cited by 50
Zhang, C., Shi, W., Sun, W., Teng, K., Dai, M., Wang, F., Chen, J., Ling, H., Ma, X., Feng, Z., et al. (2020) · Theranostics · doi:10.7150/thno.45349 · Cited by 53
“Remarkably, SEs usually bind large numbers of master transcription factors that define cell identity, and thus participate in a variety of pathophysiological processes [9, 23, 30].”
BackgroundMethodInfluentialAsada, K., Kaneko, S., Takasawa, K., Machino, H., Takahashi, S., Shinkai, N., Shimoyama, R., Komatsu, M., & Hamamoto, R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.666937 · Cited by 54
“An interesting fi nding is that disease-associated genetic mutations are particularly prevalent in super-enhancers of disease-associated cell types (100).”
BackgroundSuper-Enhancers, Phase-Separated Condensates, and 3D Genome Organization in Cancer
Tang, S. C., Vijayakumar, U., Zhang, Y., & Fullwood, M. J. (2022) · Cancers · doi:10.3390/cancers14122866 · Cited by 56
“These SE profiles can be used to identify master genes that are involved in cell identity and disease condition [2,4].”
BackgroundMultiscale 3D genome reorganization during skeletal muscle stem cell lineage progression and aging
Zhao, Y. F., Ding, Y., He, L., Zhou, Q., Chen, X., Li, Y., Alfonsi, M. V., Wu, Z., Sun, H., & Wang, H. (2023) · Science Advances · doi:10.1126/sciadv.abo1360 · Cited by 56
“SEs were identified as previously described with minor adjustment (42).”
BackgroundMethodRegulatory architecture of housekeeping genes is driven by promoter assemblies
Déjosez, M., Dall’Agnese, A., Ramamoorthy, M., Platt, J. M., Yin, X., Hogan, M. S., Brosh, R., Weintraub, A. S., Hnisz, D., Abraham, B. J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112505 · Cited by 52
“…“inner cell mass.” We found that Ronin was associated with the promoters of 10,916 genes (Table S1C) that showed a high degree of overlap with the much smaller set of previously described Ronin target genes (Figure S1A) 21,50 and, as expected, were enriched with RBMs (Figure S1B; Table S1D).”
InfluentialSelf-citationFournier, M., Bourriquen, G., Lamaze, F. C., Côté, M. C., Fournier, É., Joly-Beauparlant, C., Caron, V., Gobeil, S., Droit, A., & Bilodeau, S. (2016) · Scientific Reports · doi:10.1038/srep34962 · Cited by 55
Targeting cytokine signaling in autoimmunity: back to the future and beyond
Hirahara, K., Schwartz, D. M., Gadina, M., Kanno, Y., & O’Shea, J. J. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.10.001 · Cited by 53
Thibodeau, A., Márquez, E. J., Shin, D., Vera‐Licona, P., & Ucar, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-14389-7 · Cited by 54
“Each network node was represented using two types of data features: (1) network related and (2) genomic-data related and we built SVM-based16,17 classification models to discriminate i) broad domains from regular promoters and ii) super enhancers from regular enhancers.”
MethodStubbs, M. C., Burn, T. C., Sparks, R. B., Maduskuie, T. P., Diamond, S., Rupar, M. J., Wen, X., Volgina, A., Zolotarjova, N. I., Waeltz, P., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0098 · Cited by 51
“ZMYND11 TAF1L(2) TAF1(2) PRKCBP1 TAF1L(1) TAF1(1) PHIP(1) WDR9(1) BRWD3(1) SMARCA2 SMARCA4 PB1(5) PB1(6) PB1(4) PB1(3) PB1(1) PB1(2) CECR2 FALZ GCN5L2 PCAF”
BackgroundRegulation of Chromatin Structure During Neural Development
Kishi, Y., & Gotoh, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00874 · Cited by 51
“GAM confirmed an abundance of long-range interactions, especially between “super-enhancers” [which are marked by extremely high levels of H3K27ac (Hnisz et al., 2013; Parker et al., 2013)] in ESCs.”
BackgroundInfluentialTwohig, J. P., Figueras, A. C., Andrews, R., Wiede, F., Cossins, B. C., Soria, A. D., Lewis, M., Townsend, M. J., Millrine, D., Li, J., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0350-0 · Cited by 53
“To identify possible mechanisms that may explain this distal regulation we evaluated whether STAT1 and STAT3 peaks aligned with enhancer regions displaying enriched binding of the histone acetyl-transferase P300 (hereafter P300 enhancer elements 25, 26, 27, 28 ).”
Liu, Z., Zhang, X., Lei, H., Lam, N., Carter, S., Yockey, O., Xu, M., Mendoza, A., Hernandez, E. R., Wei, J. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14684-4 · Cited by 52
Characterization of a dual BET / HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma
Zhang, X., Zegar, T., Weiser, T., Hamdan, F. H., Berger, B., Lucas, R., Balourdas, D.-I., Ladigan, S., Cheung, P. F., Liffers, S., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33137 · Cited by 52
Yang, H., Ratnapriya, R., Cogliati, T., Kim, J.-W., & Swaroop, A. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.01.005 · Cited by 52
Bell, E., Curry, E. W., Megchelenbrink, W., Jouneau, L., Brochard, V., Tomaz, R. A., Mau, K. H. T., Atlasi, Y., de Souza, R. A., Marks, H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14916-7 · Cited by 50
3D chromatin architecture and epigenetic regulation in cancer stem cells
Feng, Y., Liu, X., & Pauklin, S. (2021) · Protein & Cell · doi:10.1007/s13238-020-00819-2 · Cited by 55
“ARCHITECTURE IN MAMMALIAN CELLS Enhancers are key cis-regulatory elements that mediate transcription regulation by converging signals from oncogenic and developmental pathways (Hnisz et al., 2015).”
BackgroundChovanec, P., Collier, A. J., Krueger, C., Várnai, C., Semprich, C. I., Schoenfelder, S., Corcoran, A. E., & Rugg‐Gunn, P. J. (2021) · Nature Communications · doi:10.1038/s41467-021-22201-4 · Cited by 48
Bobowski, M., Boulet, C., Zummo, F. P., Dubois‐Chevalier, J., Gheeraert, C., Saleh, M. B., Strub, J., Farce, A., Ploton, M., Guille, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33063-9 · Cited by 52
High-throughput Oligopaint screen identifies druggable 3D genome regulators
Park, D. S., Nguyen, S. C., Isenhart, R. L., Shah, P. P., Kim, W., Barnett, R. J., Chandra, A., Luppino, J. M., Harke, J., Wai, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06340-w · Cited by 56
Murphy, D., Salataj, E., Giammartino, D. C. D., Rodriguez-Hernaez, J., Kloetgen, A., Garg, V., Char, E., Uyehara, C. M., Ee, L.-S., Lee, U., et al. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01130-4 · Cited by 51
“1e Supplementary Table 2), consistent with the suggested role of super enhancers in cell fate regulation 58,68–70 .”
Smith, O. K., & Aladjem, M. I. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.05.027 · Cited by 51
Schwarzer, W., & Spitz, F. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.03.014 · Cited by 52
The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine
Kiani, M. T., Higgins, C. A., & Almquist, B. D. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00072 · Cited by 50
X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs
Pasque, V., Karnik, R., Chronis, C., Petrella, P. E., Langerman, J., Bonora, G., Song, J., Vanheer, L., Dimashkie, A., Meissner, A., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.03.019 · Cited by 51
“Nevertheless, we found that many CpGs, particularly those in enhancer elements, which are thought to play key roles 1548 Stem Cell Reports j Vol. 10 j 1537–1550 j May 8, 2018 for the maintenance of cell identity (Hnisz et al., 2013), change their methylation status earlier in reprogramming.”
BackgroundInfluentialNuclear pores in genome architecture and enhancer function
Pascual‐García, P., & Capelson, M. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.04.001 · Cited by 50
Zhou, J., So, K. K. H., Li, Y., Li, Y., Yuan, J., Ding, Y., Chen, F., Huang, Y., Liu, J., Lee, W., et al. (2019) · Aging Cell · doi:10.1111/acel.12996 · Cited by 52
“…example, H3K27ac enrichment is a hallmark of enhancers and is often used to define typical enhancers (TEs) and super‐enhancers (SEs) with the latter bear unusually high levels of H3K27ac and binding of key transcriptional regulators (Creyghton et al., 2010; Hnisz et al., 2013; Whyte et al., 2013).”
BackgroundMethodInfluentialThe Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies
Prager, B. C., Vasudevan, H. N., Dixit, D., Bernatchez, J. A., Wu, Q., Wallace, L. C., Bhargava, S., Lee, D., King, B. H., Morton, A. R., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0160 · Cited by 53
“A subset of enhancers marked by particularly dense and long stretches of H3K27ac signal, designated as stretch enhancers or super enhancers (SEs), highlight genes important to cell identity that require robust expression (20,23,24).”
BackgroundDynamics and function of distal regulatory elements during neurogenesis and neuroplasticityPreprint
Thakurela, S., Sahu, S. K., Garding, A., & Tiwari, V. K. (2015) · Genome Research · doi:10.1101/gr.190926.115 · Cited by 52
“Recent studies have demonstrated that super-enhancers are large clusters of transcriptional enhancers that drive the expression of genes defining cell identity (Hnisz et al. 2013; Whyte et al. 2013).”
Kolovos, P., Georgomanolis, T., Köferle, A., Larkin, J. D., Brant, L., Nikolicć, M., Gusmao, E. G., Zirkel, A., Knoch, T., van Ijcken, W. F., et al. (2016) · Genome Research · doi:10.1101/gr.210005.116 · Cited by 54
“Moreover, many enhancers regulating TNF-inducible genes are prelooped prior to stimulation, giving rise to a poised chromatin configuration (Jin et al. 2013).”
Zheng, C., Liu, M., Ge, Y., Qian, Y., & Fan, H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04563-9 · Cited by 50
Extrachromosomal circular DNA: Current status and future prospects
Zhao, Y., Yu, L., Zhang, S., Su, X., & Zhou, X. (2022) · eLife · doi:10.7554/elife.81412 · Cited by 51
Madrigal, P., Deng, S., Feng, Y., Militi, S., Goh, K. J., Nibhani, R., Grandy, R. A., Osnato, A., Ortmann, D., Brown, S. E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36116-9 · Cited by 48
Linking chromatin acylation mark-defined proteome and genome in living cells
Qin, F., Li, B., Wang, H., Ma, S., Li, J., Liu, S., Kong, L., Zheng, H., Zhu, R., Han, Y., et al. (2023) · Cell · doi:10.1016/j.cell.2023.02.007 · Cited by 55
Epigenetic Modulators as Therapeutic Agents in Cancer
Patnaik, E., Madu, C. O., & Lü, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914964 · Cited by 50
“Diseases linked to single nucleotide polymorphisms often manifest within the superenhancers of cells relevant to the specific disease [54].”
BackgroundEukaryotic enhancers: common features, regulation, and participation in diseases
Erokhin, M., Vassetzky, Y. S., Georgiev, P. G., & Chetverina, D. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1871-9 · Cited by 54
Multi-scale chromatin state annotation using a hierarchical hidden Markov model
Marco, E., Meuleman, W. R. A., Huang, J., Glass, K., Pinello, L., Wang, J., Kellis, M., & Yuan, G. (2017) · Nature Communications · doi:10.1038/ncomms15011 · Cited by 48
“Our analysis is consistent with the recent discovery that multiple regulatory elements may cluster together, spanning over 10kb regions, and cooperatively regulate cell identity 22,23,32 .”
BackgroundResultPluripotency factors functionally premark cell-type-restricted enhancers in ES cells
Kim, H. S., Tan, Y., Ma, W., Merkurjev, D., Destici, E., Ma, Q., Suter, T., Ohgi, K. A., Friedman, M. J., Skowronska‐Krawczyk, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0048-8 · Cited by 51
Reversing Mechanoinductive DSP Expression by CRISPR/dCas9–mediated Epigenome Editing
Qu, J. T., Zhu, L., Zhou, Z., Chen, P., Liu, S., Locy, M. L., Thannickal, V. J., & Zhou, Y. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201711-2242oc · Cited by 51
“Previous studies demonstrated that a vast majority of disease-associated DNA polymorphisms are mapped within DNA enhancers (28).”
BackgroundLopez‐Atalaya, J. P., Askew, K. E., Sierra, A., & Gomez‐Nicola, D. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22545 · Cited by 49
“Moreover, evidence supports that enhancers and superenhancers—large clusters of enhancers—play key roles in the acquisition and maintenance of cell identity (Rada-Iglesias et al., 2011; Hnisz et al., 2013; Whyte et al., 2013; Adam et al., 2015).”
BackgroundBlümli, S., Wiechens, N., Wu, M., Singh, V., Gierliński, M., Schweikert, G., Gilbert, N., Naughton, C., Sundaramoorthy, R., Varghese, J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109943 · Cited by 51
Mesenchymal-Type Neuroblastoma Cells Escape ALK Inhibitors
Westerhout, E. M., Hamdi, M., Stroeken, P. J. M., Nowakowska, N. E., Lakeman, A., van Arkel, J., Hasselt, N. E., Bleijlevens, B., Akogul, N., Haneveld, F., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1621 · Cited by 49
“MES and ADRN cells each have unique sets of lineage-specific super-enhancers and associated core regulatory circuitries (CRC), which are assumed to impose lineage identity (4, 5).”
BackgroundVlaming, H., Mimoso, C. A., Field, A. R., Martin, B. J. E., & Adelman, K. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00785-9 · Cited by 46
Population-level variation in enhancer expression identifies disease mechanisms in the human brain
Dong, P., Hoffman, G. E., Apontes, P., Bendl, J. M., Rahman, S., Fernando, M. B., Zeng, B., Vicari, J. M., Zhang, W., Girdhar, K., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01170-4 · Cited by 45
Epigenetic landscape reveals MECOM as an endothelial lineage regulator
Lv, J., Meng, S., Gu, Q., Zheng, R., Gao, X., Kim, J., Chen, M., Xia, B., Zuo, Y.-H., Zhu, S. L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38002-w · Cited by 45
Distal enhancers: new insights into heart development and disease
Wamstad, J. A., Wang, X., Demuren, O. O., & Boyer, L. A. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.10.008 · Cited by 48
Enhancer alterations in cancer: a source for a cell identity crisis
Kron, K. J., Bailey, S. D., & Lupien, M. (2014) · Genome Medicine · doi:10.1186/s13073-014-0077-3 · Cited by 49
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
