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Histone modifications at human enhancers reflect global cell-type-specific gene expression
Open accessAbstract
The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
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“ChIPseq using antibodies to H3K4Me3, a mark associated with active promoter sites (Ernst et al., 2011), and to H3K27Ac, a mark associated with enhancer elements (Heintzman et al., 2009), demonstrated mapped read peaks corresponding to at least four major transcriptional start sites within the SYNE1 locus (P1–P4), one of which (P3) lies immediately upstream of the p.L3206M mutation (Figure 3E).”
From Using Whole-Exome Sequencing to Identify Inherited Causes of Autism (2013) · cites this paper as Heintzman et al., 2009
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Cites
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · cited 7×
“Using previously described chromatin signatures for enhancers 5 , we predicted 36,589 enhancers in the HeLa genome (Fig.”
MethodInfluentialSelf-citationGenome-Wide Mapping of in Vivo Protein-DNA Interactions
Johnson, D. S., Mortazavi, A., Myers, R. M., & Wold, B. (2007) · Science · doi:10.1126/science.1141319 · Cited by 2,927
The ENCODE (ENCyclopedia Of DNA Elements) Project
(2004) · Science · doi:10.1126/science.1105136 · Cited by 2,390
Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., & Kellis, M. (2005) · Nature · doi:10.1038/nature03441 · Cited by 1,872
Self-citationRobertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., et al. (2007) · Nature Methods · doi:10.1038/nmeth1068 · Cited by 1,454
Genome-wide analysis of estrogen receptor binding sites
Carroll, J. S., Meyer, C. A., Song, J. S., Li, W., Geistlinger, T., Eeckhoute, J., Brodsky, A. S., Keeton, E. K., Fertuck, K. C., Hall, G., et al. (2006) · Nature Genetics · doi:10.1038/ng1901 · Cited by 1,397
Cohesin mediates transcriptional insulation by CCCTC-binding factor
Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., Tsutsumi, S., Nagae, G., Ishihara, K., Mishiro, T., et al. (2008) · Nature · doi:10.1038/nature06634 · Cited by 1,193
A Global Map of p53 Transcription-Factor Binding Sites in the Human Genome
Wei, C.-L., Wu, Q., Vega, V. B., Chiu, K. P., Ng, P., Zhang, T., Shahab, A., Yong, H. C., Fu, Y., Weng, Z., et al. (2006) · Cell · doi:10.1016/j.cell.2005.10.043 · Cited by 1,141
Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human Genome
Kim, T. H., Abdullaev, Z., Smith, A. D., Ching, K. A., Loukinov, D. I., Green, R. D., Zhang, M. Q., Lobanenkov, V. V., & Ren, B. (2007) · Cell · doi:10.1016/j.cell.2006.12.048 · Cited by 1,022
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Flagged first, then by citations
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Items 101–200 of 1,009
Functional and topological characteristics of mammalian regulatory domains
Symmons, O., Uslu, V. V., Tsujimura, T., Ruf, S., Nassari, S., Schwarzer, W., Ettwiller, L., & Spitz, F. (2014) · Genome Research · doi:10.1101/gr.163519.113 · Cited by 455
Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451
An encyclopedia of mouse DNA elements (Mouse ENCODE)
Mouse ENCODE Consortium, Stamatoyannopoulos, J. A., Snyder, M., Hardison, R., Ren, B., Gingeras, T., Gilbert, D. M., Groudine, M., Bender, M., Kaul, R., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-8-418 · Cited by 446
Self-citationUsing Whole-Exome Sequencing to Identify Inherited Causes of Autism
Yu, T. W., Chahrour, M. H., Coulter, M. E., Jiralerspong, S., Okamura-Ikeda, K., Ataman, B., Schmitz-Abe, K., Harmin, D. A., Adli, M., Malik, A. N., et al. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.002 · Cited by 442
PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
Liu, W., Tanasa, B., Tyurina, O. V., Zhou, T. Y., Gassmann, R., Liu, W. T., Ohgi, K. A., Benner, C., Garcia-Bassets, I., Aggarwal, A. K., et al. (2010) · Nature · doi:10.1038/nature09272 · Cited by 441
Jolma, A., Kivioja, T., Toivonen, J., Cheng, L., Wei, G., Enge, M., Taipale, M., Vaquerizas, J. M., Yan, J., Sillanpää, M. J., et al. (2010) · Genome Research · doi:10.1101/gr.100552.109 · Cited by 441
Principles for the post-GWAS functional characterization of cancer risk loci
Freedman, M. L., Monteiro, Á. N. A., Gayther, S. A., Coetzee, G. A., Risch, A., Plass, C., Casey, G., Biasi, M. D., Carlson, C., Duggan, D. J., et al. (2011) · Nature Genetics · doi:10.1038/ng.840 · Cited by 442
Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Gifford, C. A., Ziller, M. J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A. K., Kelley, D. R., Shishkin, A. A., Issner, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.037 · Cited by 435
Self-citationStanczyk, F. Z., Hapgood, J. P., Winer, S., & Mishell, D. R. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1008 · Cited by 429
Qi, T., Wu, Y., Zeng, J., Zhang, F., Xue, A., Jiang, L., Zhu, Z., Kemper, K., Yengo, L., Zheng, Z., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04558-1 · Cited by 427
The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers
Alver, B. H., Kim, K. H., Lu, P., Wang, X., Manchester, H. E., Wang, W., Haswell, J. R., Park, P. J., & Roberts, C. W. M. (2017) · Nature Communications · doi:10.1038/ncomms14648 · Cited by 427
Identification of Genetic Variants That Affect Histone Modifications in Human Cells
McVicker, G., van de Geijn, B., Degner, J. F., Cain, C. E., Banovich, N. E., Raj, A., Lewellen, N., Myrthil, M., Gilad, Y., & Pritchard, J. K. (2013) · Science · doi:10.1126/science.1242429 · Cited by 436
ChIP-Seq identification of weakly conserved heart enhancers
Blow, M. J., McCulley, D. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., et al. (2010) · Nature Genetics · doi:10.1038/ng.650 · Cited by 392
Self-citationA method to predict the impact of regulatory variants from DNA sequence
Lee, D., Gorkin, D. U., Baker, M., Strober, B. J., Asoni, A. L., McCallion, A. S., & Beer, M. (2015) · Nature Genetics · doi:10.1038/ng.3331 · Cited by 430
CD4 + T-cell subsets in inflammatory diseases: beyond the T h 1/T h 2 paradigm
Hirahara, K., & Nakayama, T. (2016) · International Immunology · doi:10.1093/intimm/dxw006 · Cited by 417
Zhou, K., Liu, S., Sun, W., Zheng, L., Zhou, H., Yang, J., & Qu, L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw965 · Cited by 417
YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers
Stein, C., Bardet, A. F., Roma, G., Bergling, S., Clay, I., Ruchti, A., Agarinis, C., Schmelzle, T., Bouwmeester, T., Schübeler, D., et al. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1005465 · Cited by 414
Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia
Trimarchi, T., Bilal, E., Ntziachristos, P., Fabbri, G., Dalla‐Favera, R., Tsirigos, A., & Aifantis, I. (2014) · Cell · doi:10.1016/j.cell.2014.05.049 · Cited by 426
seqMINER: an integrated ChIP-seq data interpretation platform
Ye, T., Krebs, A. R., Choukrallah, M.-A., Keime, C., Plewniak, F., Davidson, I., & Tora, L. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1287 · Cited by 432
Amit, I., Winter, D. R., & Jung, S. (2015) · Nature Immunology · doi:10.1038/ni.3325 · Cited by 416
Brd4 and JMJD6-Associated Anti-Pause Enhancers in Regulation of Transcriptional Pause Release
Liu, W., Ma, Q., Wong, K., Li, W., Ohgi, K., Zhang, J., Aggarwal, A. K., & Rosenfeld, M. G. (2013) · Cell · doi:10.1016/j.cell.2013.10.056 · Cited by 421
STAT3 signaling controls satellite cell expansion and skeletal muscle repair
Tierney, M. T., Aydogdu, T., Sala, D., Malecova, B., Gatto, S., Puri, P. L., Latella, L., & Sacco, A. (2014) · Nature Medicine · doi:10.1038/nm.3656 · Cited by 401
Epigenetics and cardiovascular disease
Ordovás, J. M., & Smith, C. E. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.104 · Cited by 413
Noncoding Transcription at Enhancers: General Principles and Functional Models
Natoli, G., & Andrau, J. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155459 · Cited by 418
Iwafuchi-Doi, M., Donahue, G., Kakumanu, A., Watts, J. A., Mahony, S., Pugh, B. F., Lee, D., Kaestner, K. H., & Zaret, K. S. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.001 · Cited by 390
Herz, H.-M., Mohan, M., Garruss, A. S., Liang, K., Takahashi, Y.-H., Mickey, K., Voets, O., Verrijzer, C. P., & Shilatifard, A. (2012) · Genes & Development · doi:10.1101/gad.201327.112 · Cited by 388
The role of enhancers in cancer
Sur, I., & Taipale, J. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.62 · Cited by 393
MicroRNAs activate gene transcription epigenetically as an enhancer trigger
Xiao, M., Li, J., Li, W., Wang, Y., Wu, F., Xi, Y., Zhang, L., Ding, C., Luo, H., Li, Y., et al. (2016) · RNA Biology · doi:10.1080/15476286.2015.1112487 · Cited by 396
Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development
Nord, A. S., Blow, M. J., Attanasio, C., Akiyama, J. A., Holt, A., Hosseini, R., Phouanenavong, S., Plajzer-Frick, I., Shoukry, M., Afzal, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.033 · Cited by 375
The Drosophila embryo at single-cell transcriptome resolution
Karaiskos, N., Wahle, P., Alles, J., Boltengagen, A., Ayoub, S., Kipar, C., Kocks, C., Rajewsky, N., & Zinzen, R. P. (2017) · Science · doi:10.1126/science.aan3235 · Cited by 382
Grundberg, E., Meduri, E., Sandling, J. K., Hedman, Å. K., Keildson, S., Buil, A., Busche, S., Yuan, W., Nisbet, J., Sekowska, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.10.004 · Cited by 370
Cis-acting noncoding RNAs: friends and foes
Guil, S., & Esteller, M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2428 · Cited by 382
Enhancer RNAs are an important regulatory layer of the epigenome
Sartorelli, V., & Lauberth, S. M. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0446-0 · Cited by 380
GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibilityPreprint
Theodorou, V., Stark, R., Menon, S., & Carroll, J. S. (2012) · Genome Research · doi:10.1101/gr.139469.112 · Cited by 367
Methylation-Dependent and -Independent Genomic Targeting Principles of the MBD Protein Family
Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D. (2013) · Cell · doi:10.1016/j.cell.2013.03.011 · Cited by 365
STATs Shape the Active Enhancer Landscape of T Cell Populations
Vahedi, G., Takahashi, H., Nakayamada, S., Sun, H., Sartorelli, V., Kanno, Y., & O’Shea, J. J. (2012) · Cell · doi:10.1016/j.cell.2012.09.044 · Cited by 380
H3K4 tri‐methylation provides an epigenetic signature of active enhancers
Pękowska, A., Benoukraf, T., Cabeza, J. Z., Belhocine, M., Koch, F., Holota, H., Imbert, J., Andrau, J., Ferrier, P., & Spicuglia, S. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.295 · Cited by 390
Locus-specific editing of histone modifications at endogenous enhancers
Mendenhall, E. M., Williamson, K. E., Reyon, D., Zou, J., Ram, O., Joung, J. K., & Bernstein, B. (2013) · Nature Biotechnology · doi:10.1038/nbt.2701 · Cited by 371
DNA methylation changes in plasticity genes accompany the formation and maintenance of memory
Halder, R., Hennion, M., Vidal, R. O., Shomroni, O., Rahman, R.-U., Rajput, A., Centeno, T. P., van Bebber, F., Capece, V., Vizcaino, J. C. G., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4194 · Cited by 358
Ahmadiyeh, N., Pomerantz, M. M., Grisanzio, C., Herman, P. K., Li, J., Almendro, V., He, H. H., Brown, M. A., Liu, X. S., Davis, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910668107 · Cited by 363
A CTCF-independent role for cohesin in tissue-specific transcriptionPreprint
Schmidt, D., Schwalie, P. C., Ross-Innes, C. S., Hurtado, A., Brown, G. D., Carroll, J. S., Flicek, P., & Odom, D. T. (2010) · Genome Research · doi:10.1101/gr.100479.109 · Cited by 370
Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues
Ernst, J., & Kellis, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3157 · Cited by 357
Self-citationMorgan, M. A., & Shilatifard, A. (2020) · Nature Genetics · doi:10.1038/s41588-020-00736-4 · Cited by 374
Cotney, J., Muhle, R. A., Sanders, S. J., Liu, L., Willsey, A. J., Niu, W., Liu, W., Klei, L., Lei, J., Yin, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7404 · Cited by 350
Sallari, R. C., Zhang, X., Wright, J. B., Bailey, S. D., Cole, M. D., Eeckhoute, J., Moore, J. H., & Lupien, M. (2012) · Nature Genetics · doi:10.1038/ng.2416 · Cited by 354
Self-citationLive-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
Alexander, J. M., Guan, J., Li, B., Maliskova, L., Song, M., Shen, Y., Huang, B., Lomvardas, S., & Weiner, O. D. (2019) · eLife · doi:10.7554/elife.41769 · Cited by 346
CTCF and Cohesin: Linking Gene Regulatory Elements with Their Targets
Merkenschlager, M., & Odom, D. T. (2013) · Cell · doi:10.1016/j.cell.2013.02.029 · Cited by 345
Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O'Shea, J. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075058 · Cited by 342
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Marand, A. P., Eveland, A. L., Kaufmann, K., & Springer, N. M. (2023) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-070122-030236 · Cited by 346
GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
Study, A. C., Pharoah, P. D. P., Australian Ovarian Cancer Study Group, Tsai, Y.-Y., Ramus, S. J., Phelan, C. M., Goode, E. L., Lawrenson, K., Buckley, M. A., Fridley, B. L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2564 · Cited by 344
Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
Zhang, X., Choi, P. S., Francis, J. M., Imielinski, M. B., Watanabe, H., Cherniack, A. D., & Meyerson, M. M. (2015) · Nature Genetics · doi:10.1038/ng.3470 · Cited by 348
Self-citationReplication landscape of the human genome
Petryk, N., Kahli, M., d’Aubenton-Carafa, Y., Jaszczyszyn, Y., Shen, Y., Silvain, M., Thermes, C., Chen, C.-L., & Hyrien, O. (2016) · Nature Communications · doi:10.1038/ncomms10208 · Cited by 340
Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer
Akhtar‐Zaidi, B., Sallari, R. C., Corradin, O., Saiakhova, A., Bartels, C. F., Balasubramanian, D., Myeroff, L. L., Lutterbaugh, J., Jarrar, A., Kalady, M. F., et al. (2012) · Science · doi:10.1126/science.1217277 · Cited by 337
The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers
Amos, C. I., Dennis, J., Wang, Z., Byun, J., Schumacher, F. R., Gayther, S. A., Casey, G., Hunter, D. J., Sellers, T. A., Gruber, S. B., et al. (2016) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-16-0106 · Cited by 342
FunSeq2: A framework for prioritizing noncoding regulatory variants in cancer
Fu, Y., Liu, Z., Lou, S., Bedford, J., Mu, X. J., Yip, K. Y.-L., Khurana, E., & Gerstein, M. (2014) · Genome biology · doi:10.1186/s13059-014-0480-5 · Cited by 341
ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours
Chi, P., Chen, Y., Zhang, L., Guo, X., Wongvipat, J., Shamu, T., Fletcher, J. A., Dewell, S. B., Maki, R. G., Zheng, D., et al. (2010) · Nature · doi:10.1038/nature09409 · Cited by 333
A Comprehensive Map of Insulator Elements for the Drosophila Genome
Nègre, N., Brown, C. D., Shah, P. K., Kheradpour, P., Morrison, C. A., Henikoff, J. G., Feng, X., Ahmad, K., Russell, S. R. H., White, R. A., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000814 · Cited by 341
Self-citationTranscription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters
Koch, F., Fenouil, R., Gut, M., Cauchy, P., Albert, T., Cabeza, J. Z., Spicuglia, S., de la Chapelle, A. L., Heidemann, M., Hintermair, C., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2085 · Cited by 333
Hon, G. C., Song, C., Du, T., Jin, F., Selvaraj, S., Lee, A. Y., Yen, C., Ye, Z., Mao, S.-Q., Wang, B.-A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.026 · Cited by 349
Self-citationThe origin of Metazoa: a unicellular perspective
Sebé-Pedrós, A., Degnan, B. M., & Ruiz-Trillo, I. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.21 · Cited by 332
Architectural and Functional Commonalities between Enhancers and Promoters
Kim, T.-K., & Shiekhattar, R. (2015) · Cell · doi:10.1016/j.cell.2015.08.008 · Cited by 354
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Papp, B., & Plath, K. (2013) · Cell · doi:10.1016/j.cell.2013.02.043 · Cited by 307
Sekrecka, A., Błaszczyk, K., Wesoły, J., & Bluyssen, H. A. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01135 · Cited by 333
Chromatin Position Effects Assayed by Thousands of Reporters Integrated in Parallel
Akhtar, W., de Jong, J., Pindyurin, A. V., Pagie, L., Meuleman, W. R. A., de Ridder, J., Berns, A. J. M., Wessels, L. F. A., van Lohuizen, M., & van Steensel, B. (2013) · Cell · doi:10.1016/j.cell.2013.07.018 · Cited by 338
Modulation of tissue repair by regeneration enhancer elements
Kang, J., Hu, J., Karra, R., Dickson, A. L., Tornini, V. A., Nachtrab, G. T., Gemberling, M. P., Goldman, J., Black, B. L., & Poss, K. D. (2016) · Nature · doi:10.1038/nature17644 · Cited by 326
Kheradpour, P., Ernst, J., Melnikov, A., Rogov, P., Wang, L., Zhang, X., Alston, J., Mikkelsen, T. S., & Kellis, M. (2013) · Genome Research · doi:10.1101/gr.144899.112 · Cited by 315
Self-citationSET for life: biochemical activities and biological functions of SET domain-containing proteins
Herz, H.-M., Garruss, A., & Shilatifard, A. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.09.004 · Cited by 314
Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest
Rada-Iglesias, A., Bajpai, R., Prescott, S., Brugmann, S. A., Swigut, T., & Wysocka, J. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.07.006 · Cited by 314
Epigenetics, plasticity, and evolution: How do we link epigenetic change to phenotype?
Duncan, E. J., Gluckman, P. D., & Dearden, P. K. (2014) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.22571 · Cited by 329
Genome-wide remodeling of the epigenetic landscape during myogenic differentiation
Asp, P., Blum, R., Vethantham, V., Parisi, F., Micsinai, M., Cheng, J., Bowman, C., Kluger, Y., & Dynlacht, B. D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102223108 · Cited by 324
Enhancer biology and enhanceropathies
Smith, E. R., & Shilatifard, A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2784 · Cited by 326
Histone Acetylome-wide Association Study of Autism Spectrum Disorder
Sun, W., Poschmann, J., Cruz-Herrera del Rosario, R., Parikshak, N. N., Hajan, H. S., Kumar, V., Ramasamy, R., Belgard, T. G., Elanggovan, B., Wong, C. C. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.031 · Cited by 306
Trompouki, E., Bowman, T. V., Lawton, L. N., Fan, Z. P., Wu, D.-C., DiBiase, A., Martin, C., Cech, J. N., Sessa, A. K., LeBlanc, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.044 · Cited by 317
Romano, R., Smalley, K., Magraw, C. B. L., Serna, V. A., Kurita, T., Raghavan, S., & Sinha, S. (2012) · Development · doi:10.1242/dev.071191 · Cited by 308
Fort, A., Hashimoto, K., Yamada, D., Salimullah, M., Keya, C. A., Saxena, A., Bonetti, A., Voineagu, I., Bertin, N., Kratz, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.2965 · Cited by 314
ISMARA: automated modeling of genomic signals as a democracy of regulatory motifsPreprint
Balwierz, P. J., Pachkov, M. V., Arnold, P., Gruber, A. J., Zavolan, M., & van Nimwegen, E. (2014) · Genome Research · doi:10.1101/gr.169508.113 · Cited by 306
Bivalent histone modifications in early embryogenesis
Vastenhouw, N. L., & Schier, A. F. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.03.009 · Cited by 315
Akalin, A., Garrett-Bakelman, F. E., Kormaksson, M., Busuttil, J., Zhang, L., Khrebtukova, I., Milne, T. A., Huang, Y., Biswas, D., Hess, J. L., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002781 · Cited by 296
TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages
Silva, T. C., Colaprico, A., Olsen, C., D’Angelo, F., Bontempi, G., Ceccarelli, M., & Noushmehr, H. (2016) · F1000Research · doi:10.12688/f1000research.8923.1 · Cited by 303
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 301
Ilott, N. E., Heward, J. A., Roux, B. T., Tsitsiou, E., Fenwick, P. S., Lenzi, L., Goodhead, I., Hertz‐Fowler, C., Heger, A., Hall, N., et al. (2014) · Nature Communications · doi:10.1038/ncomms4979 · Cited by 297
Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity
Phan, A. T., Goldrath, A. W., & Glass, C. K. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.016 · Cited by 296
YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers
Galli, G. G., Carrara, M., Yuan, W.-C., Valdes-Quezada, C., Gurung, B., Pepe-Mooney, B., Zhang, T., Geeven, G., Gray, N. S., de Laat, W., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.001 · Cited by 290
RNA sequencing reveals two major classes of gene expression levels in metazoan cells
Hebenstreit, D., Fang, M., Gu, M., Charoensawan, V., van Oudenaarden, A., & Teichmann, S. A. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.28 · Cited by 289
Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation
Kubo, N., Ishii, H., Xiong, X., Bianco, S., Meitinger, F., Hu, R., Hocker, J. D., Conte, M., Gorkin, D., Yu, M., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-00539-5 · Cited by 289
Self-citationEnhancers as information integration hubs in development: lessons from genomics
Buecker, C., & Wysocka, J. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.02.008 · Cited by 295
Jadhav, U., Saxena, M., O’Neill, N. K., Saadatpour, A., Yuan, G., Herbert, Z. T., Murata, K., & Shivdasani, R. A. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.05.001 · Cited by 296
Oler, A. J., Alla, R., Roberts, D. N., Wong, A., Hollenhorst, P. C., Chandler, K. J., Cassiday, P. A., Nelson, C. A., Hagedorn, C. H., Graves, B. J., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1801 · Cited by 293
Single-cell epigenomics: techniques and emerging applications
Schwartzman, O., & Tanay, A. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3980 · Cited by 291
Chen, Y., Chi, P., Rockowitz, S., Iaquinta, P. J., Shamu, T., Shukla, S., Gao, D., Sirota, I., Carver, B. S., Wongvipat, J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3216 · Cited by 289
High-resolution interrogation of functional elements in the noncoding genome
Sanjana, N. E., Wright, J. B., Zheng, K., Shalem, O., Fontanillas, P., Joung, J., Cheng, C. S., Regev, A., & Zhang, F. (2016) · Science · doi:10.1126/science.aaf7613 · Cited by 290
CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas
Jiang, Y., Ortega-Molina, A., Geng, H., Ying, H.-Y., Hatzi, K., Parsa, S., McNally, D., Wang, L., Doane, A. S., Agirre, X., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0975 · Cited by 278
Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1APreprint
Macfarlan, T. S., Gifford, W. D., Agarwal, S., Driscoll, S. P., Lettieri, K., Wang, J., Andrews, S. E., Franco, L., Rosenfeld, M. G., Ren, B., et al. (2011) · Genes & Development · doi:10.1101/gad.2008511 · Cited by 288
Self-citationGenome-wide map of regulatory interactions in the human genome
Heidari, N., Phanstiel, D. H., He, C., Grubert, F., Jahanbani, F., Kasowski, M., Zhang, M. Q., & Snyder, M. P. (2014) · Genome Research · doi:10.1101/gr.176586.114 · Cited by 278
Advanced Applications of RNA Sequencing and Challenges
Han, Y., Gao, S., Muegge, K., Zhang, W., & Zhou, B. (2015) · Bioinformatics and Biology Insights · doi:10.4137/bbi.s28991 · Cited by 303
Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance
Takahashi, N., Chen, H., Harris, I. S., Stover, D. G., Selfors, L. M., Bronson, R. T., Raedt, T. D., Cichowski, K. M., Welm, A. L., Mori, Y., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.001 · Cited by 282
The functional diversity of protein lysine methylation
Lanouette, S., Mongeon, V., Figeys, D., & Couture, J. (2014) · Molecular Systems Biology · doi:10.1002/msb.134974 · Cited by 285
Maher, K. A., Bajic, M., Kajala, K., Reynoso, M. A., Pauluzzi, G. C., West, D. A., Zumstein, K., Woodhouse, M. R., Bubb, K. L., Dorrity, M. W., et al. (2017) · The Plant Cell · doi:10.1105/tpc.17.00581 · Cited by 277
Decoding enhancers using massively parallel reporter assays
Inoue, F., & Ahituv, N. (2015) · Genomics · doi:10.1016/j.ygeno.2015.06.005 · Cited by 272
Stimulus-specific combinatorial functionality of neuronal c-fos enhancers
Joo, J.-Y., Schaukowitch, K., Farbiak, L., Kilaru, G., & Kim, T.-K. (2016) · Nature Neuroscience · doi:10.1038/nn.4170 · Cited by 271
Metadata
- Authors
- Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., Ching, K. A., Antosiewicz-Bourget, J. E., Liu, H., Zhang, X., Green, R. D., Lobanenkov, V. V., Stewart, R., Thomson, J. A., Crawford, G. E., Kellis, M., & Ren, B.
- Affiliations
- Ludwig Cancer Research (BE)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Broad Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
- Morgridge Institute for Research (US)
- University of Wisconsin–Madison (US)
- Duke University (US)
- Corresponding author
- Ren, Bing
- ORCID
- Venue
- Nature
- Published
- 2009-03-18
- Volume
- 459
- Issue
- 7243
- Pages
- 108-112
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2910248
- OpenAlex
- W2123564569
- Cited by
- 2,533
- References
- 27
- Citations by year
- 2026: 56 · 2025: 101 · 2024: 115 · 2023: 122 · 2022: 101 · 2021: 126 · 2020: 171 · 2019: 150 · 2018: 163 · 2017: 154 · 2016: 164 · 2015: 183 · 2014: 193 · 2013: 204 · 2012: 188
- FWCI
- 71.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PubMed Central
- Funders
- National Institutes of Health
- National Human Genome Research Institute (U01HG003151, R01HG004037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- histone modifications, enhancers, cell type-specific gene expression, promoter, insulators, CTCF binding, chromatin state, cis-regulatory elements, human cell lines, ChIP-chip
- MeSH terms
- Binding Sites, Cell Line, Cell Physiological Phenomena, Chromatin, Gene Expression Regulation, HeLa Cells, Histones, Humans, Promoter Regions, Genetic, Transcription Factors, Genome, Human, K562 Cells
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