Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers

References

• Heinz S, Romanoski CE, Benner C, et al. The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol. 2015;16:144–154.
   PubMed Web of Science ®Google Scholar
• Barolo S. Shadow enhancers: frequently asked questions about distributed cis-regulatory information and enhancer redundancy. BioEssays. 2012;34:135–141.
   PubMed Web of Science ®Google Scholar
• Thurman RE, Rynes E, Humbert R, et al. The accessible chromatin landscape of the human genome. Nature. 2012;489:75–82.
   PubMed Web of Science ®Google Scholar
• Heintzman ND, Hon GC, Hawkins RD, et al. Histone modifications at human enhancers reflect global cell type-specific gene expression. Nature. 2009;459:108–112.
   PubMed Web of Science ®Google Scholar
• Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet. 2014;15:272–286.
   PubMed Web of Science ®Google Scholar
• Rada-Iglesias A, Bajpai R, Swigut T, et al. A unique chromatin signature uncovers early developmental enhancers in humans. Nature. 2011;470:279–283.
   PubMed Web of Science ®Google Scholar
• Arnold CD, Gerlach D, Stelzer C, et al. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science. 2013;339:1074–1077.
   PubMed Web of Science ®Google Scholar
• Bonn S, Zinzen RP, Girardot C, et al. Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat Genet. 2012;44:148–156.
   PubMed Web of Science ®Google Scholar
• Kim T-K, Hemberg M, Gray JM, et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010;465:182–187.
   PubMed Web of Science ®Google Scholar
• Visel A, Mj B, Li Z, et al. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature. 2009;457:854–858.
   PubMed Web of Science ®Google Scholar
• Calo E, Wysocka J. Modification of enhancer chromatin: what, how, and why? Mol Cell. 2013;49:825–837.
   PubMed Web of Science ®Google Scholar
• Chen K, Chen Z, Wu D, et al. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. 2015;47:1149–1157.
   PubMed Web of Science ®Google Scholar
• Benayoun BA, Pollina EA, Ucar D, et al. H3K4me3 breadth is linked to cell identity and transcriptional consistency. Cell. 2014;158:673–688.
   PubMed Web of Science ®Google Scholar
• Dincer A, Gavin DP, Xu K, et al. Deciphering H3K4me3 broad domains associated with gene-regulatory networks and conserved epigenomic landscapes in the human brain. Transl Psychiatry. 2015;5:e679.
   PubMed Web of Science ®Google Scholar
• Creyghton MP, Cheng AW, Welstead GG, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010;107:21931–21936.
   PubMed Web of Science ®Google Scholar
• Whyte WA, Orlando DA, Hnisz D, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013;153:307–319.
   PubMed Web of Science ®Google Scholar
• Hnisz D, Abraham BJ, Lee TI, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155:934–947.
   PubMed Web of Science ®Google Scholar
• Lovén J, Hoke HA, Cy L, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell. 2013;153:320–334.
   PubMed Web of Science ®Google Scholar
• Suzuki HI, Young RA, Sharp PA. Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis. Cell. 2017;168:1000–1014.e15.
   PubMed Web of Science ®Google Scholar
• Heyn H, Vidal E, Ferreira HJ, et al. Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer. Genome Biol. 2016;17:11.
   PubMed Web of Science ®Google Scholar
• Parker SCJ, Stitzel ML, Taylor DL, et al. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proc Natl Acad Sci U S A. 2013;110:17921–17926.
   PubMed Web of Science ®Google Scholar
• Quang DX, Erdos MR, Parker SCJ, et al. Motif signatures in stretch enhancers are enriched for disease-associated genetic variants. Epigenetics Chromatin. 2015;8:23.
   PubMed Web of Science ®Google Scholar
• Li Q, Peterson KR, Fang X, et al. Locus control regions. Blood. 2002;100:3077–3086.
   PubMed Web of Science ®Google Scholar
• Vahedi G, Kanno Y, Furumoto Y, et al. Super-enhancers delineate disease-associated regulatory nodes in T cells. Nature. 2015;520:558–562.
   PubMed Web of Science ®Google Scholar
• Hnisz D, Schuijers J, Lin CY, et al. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. Mol Cell. 2015;58:362–370.
   PubMed Web of Science ®Google Scholar
• Flynn RA, Do BT, Rubin AJ, et al. 7SK-BAF axis controls pervasive transcription at enhancers. Nat Struct Mol Biol. 2016;23:1–11.
   PubMed Web of Science ®Google Scholar
• Niederriter A, Varshney A, Parker S, et al. Super enhancers in cancers, complex disease, and developmental disorders. Genes. 2015;6:1183–1200.
   PubMed Web of Science ®Google Scholar
• Pott S, Lieb JD. What are super-enhancers? Nat Genet. 2014;47:8–12.
   Web of Science ®Google Scholar
• Khan A, Zhang X. dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic Acids Res. 2016;44:D164–D171.
   PubMed Web of Science ®Google Scholar
• Rosenbloom KR, Armstrong J, Barber GP, et al. The UCSC Genome Browser database: 2015 update. Nucleic Acids Res. 2014;43:D670–D681.
   PubMed Web of Science ®Google Scholar
• Dunham I, Kundaje A, Aldred SF, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.
   PubMed Web of Science ®Google Scholar
• Pasquali L, Gaulton KJ, Rodríguez-Seguí SA, et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat Genet. 2014;46:136–143.
   PubMed Web of Science ®Google Scholar
• Morris AP, Voight BF, Teslovich TM, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44:981–990.
   PubMed Web of Science ®Google Scholar
• Scott RA, Lagou V, Welch RP, et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012;44:991–1005.
   PubMed Web of Science ®Google Scholar
• Rao SSP, Huang S-C, Hilaire BGS, et al. Cohesin loss eliminates all loop domains. Cell. 2017;171:305–320.e24.
   PubMed Web of Science ®Google Scholar
• Zuin J, Dixon JR, Mija VDR, et al. Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci USA. 2014;111:996–1001.
   PubMed Web of Science ®Google Scholar
• Andersson R, Gebhard C, Miguel-Escalada I, et al. An atlas of active enhancers across human cell types and tissues. Nature. 2014;507:455–461.
   PubMed Web of Science ®Google Scholar
• Core LJ, Waterfall JJ, Lis JT. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science. 2008;322:1845–1848.
   PubMed Web of Science ®Google Scholar
• Kruesi WS, Core LJ, Waters CT, et al. Condensin controls recruitment of RNA polymerase II to achieve nematode X-chromosome dosage compensation. eLife. 2013;2:e00808.
   PubMed Web of Science ®Google Scholar
• Mikhaylichenko O, Bondarenko V, Harnett D, et al. The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes Dev. 2018;32:42–57.
   PubMed Web of Science ®Google Scholar
• Henriques T, Scruggs BS, Inouye MO, et al. Widespread transcriptional pausing and elongation control at enhancers. Genes Dev. 2018;32:26–41.
   PubMed Web of Science ®Google Scholar
• Rennie S, Dalby M, Lloret-Llinares M, et al. Transcription start site analysis reveals widespread divergent transcription in D. melanogaster and core promoter-encoded enhancer activities. Nucleic Acids Res. 2018;46:5455–5469.
   PubMed Web of Science ®Google Scholar
• Ernst J, Kheradpour P, Mikkelsen TS, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473:43–49.
   PubMed Web of Science ®Google Scholar
• Dukler N, Gulko B, Huang Y, et al. Is a super-enhancer greater than the sum of its parts? Nat Genet. 2017;49:2–7.
   Web of Science ®Google Scholar
• Proudhon C, Snetkova V, Raviram R, et al. Active and inactive enhancers cooperate to exert localized and long-range control of gene regulation. Cell Rep. 2016;15:2159–2169.
   PubMed Web of Science ®Google Scholar
• Shin HY, Willi M, Yoo KH, et al. Hierarchy within the mammary STAT5-driven wap super-enhancer. Nat Genet. 2016;48:904–911.
   PubMed Web of Science ®Google Scholar
• Hay D, Hughes JR, Babbs C, et al. Genetic dissection of the α-globin super-enhancer in vivo. Nat Genet. 2016;48:1–12.
   Web of Science ®Google Scholar
• Andersson R. Promoter or enhancer, what’s the difference? Deconstruction of established distinctions and presentation of a unifying model. BioEssays. 2015;37:314–323.
   PubMed Web of Science ®Google Scholar
• Andersson R, Sandelin A, Danko CG. A unified architecture of transcriptional regulatory elements. Trends Genet. 2015;31:426–433.
   PubMed Web of Science ®Google Scholar
• Hnisz D, Shrinivas K, Ra Y, et al. A phase separation model for transcriptional control. Cell. 2017;169:13–23.
   PubMed Web of Science ®Google Scholar
• Langmead B, Trapnell C, Pop M, et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10:R25.
   PubMed Web of Science ®Google Scholar
• Ong C-T, Corces VG. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet. 2011;12:283–293.
   PubMed Web of Science ®Google Scholar
• Chepelev I, Wei G, Wangsa D, et al. Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization. Cell Res. 2012;22:490–503.
   PubMed Web of Science ®Google Scholar
• Dixon JR, Selvaraj S, Yue F, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485:376–380.
   PubMed Web of Science ®Google Scholar
• McLean CY, Bristor D, Hiller M, et al. GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol. 2010;28:495–501.
   PubMed Web of Science ®Google Scholar
• Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–842.
   PubMed Web of Science ®Google Scholar
• Khan A, Mathelier A. Intervene: a tool for intersection and visualization of multiple gene or genomic region sets. BMC Bioinformatics. 2017;18:287.
   PubMed Web of Science ®Google Scholar
• Shen L, Shao N, Liu X, et al. ngs.plot: quick mining and visualization of next-generation sequencing data by integrating genomic databases. BMC genomics. BMC Genomics. 2014;15:284.
   PubMed Web of Science ®Google Scholar
• Down TA, Piipari M, Hubbard TJP. Dalliance: interactive genome viewing on the web. Bioinformatics. 2011;27:889–890.
   PubMed Web of Science ®Google Scholar