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Histone H3K27ac separates active from poised enhancers and predicts developmental state
Open accessAbstract
Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although enhancer elements are known to be associated with certain histone modifications and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. This indicates that the amount of actively used enhancers is lower than previously anticipated. Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming.
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“providing support for the upstream region being an enhancer element that becomes active upon TLR-4 activation (Creyghton et al., 2010).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Creyghton et al., 2010
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“Currently mono-methylation of histone H3 lysine 4 (H3K4me1), associated with the binding of Trithorax/MLL complexes, is taken to be the hallmark of both ‘primed’ and active enhancers, whilst active enhancers additionally tend to associate with the acetylation of histone H3 lysine 27 (H3K27ac) [133–137].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [133]
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“In the cerebral cortex, rs1057233- and rs78245530-harboring regions exhibited enhancer activity (indicated by the low H3K4me3 signal and high H3K27ac signal [45]) (Fig. 2d).”
From Association of SPI1 haplotypes with altered SPI1 gene expression and Alzheimer’s disease risk (2022) · cites this paper as [45]
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“Monomethylation on H3K4 (H3K4me1) in combination with acetylation of H3 at K27 (H3K27ac) designates the active enhancer state33 while H3K4me1 alone, or with trimethylation of H3K27 (H3K27me3), defines a primed or repressed enhancer, respectively30.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [33]
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“Assisted loading events are coupled with increases in enhancer activity as measured by DNase hypersensitivity or H3K27 acetylation (H3K27ac), two well-established markers for active enhancers38–40.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [39]
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Cites
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Self-citationHeintzman, 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 2×
“For instance, the histone acetyltransferase p300 has been used as a reliable marker to identify distal enhancers (10, 11, 16) and in agreement with this could be found associated with a significant portion of H3K4me1-enriched regions (Fig.”
BackgroundMethodGenome-scale DNA methylation maps of pluripotent and differentiated cells
Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., et al. (2008) · Nature · doi:10.1038/nature07107 · Cited by 2,536
Self-citationHistone modifications at human enhancers reflect global cell-type-specific gene expression
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., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
Combinatorial patterns of histone acetylations and methylations in the human genome
Wang, Z., Zang, C., Rosenfeld, J. A., Schones, D. E., Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Peng, W., Zhang, M. Q., et al. (2008) · Nature Genetics · doi:10.1038/ng.154 · Cited by 2,331
From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus
Musunuru, K., Strong, A., Frank-Kamenetsky, M., Lee, N. E., Ahfeldt, T., Sachs, K. V., Li, X., Li, H., Kuperwasser, N., Ruda, V. M., et al. (2010) · Nature · doi:10.1038/nature09266 · Cited by 1,140
Ghisletti, S., Barozzi, I., Mietton, F., Polletti, S., De Santa, F., Venturini, E., Gregory, L., Lonie, L., Chew, A., Wei, C.-L., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.02.008 · Cited by 666
Genomic views of distant-acting enhancers
Visel, A., Rubin, E. M., & Pennacchio, L. A. (2009) · Nature · doi:10.1038/nature08451 · Cited by 610
Research works printed but not linked: 22
- ND Heintzman, B Ren, Finding distal regulatory elements in the human genome. Curr Opin Genet Dev 19, 541–549 (2009). · DOI
- M Bulger, M Groudine, Looping versus linking: Toward a model for long-distance gene activation. Genes Dev 13, 2465–2477 (1999). · DOI
- D Boffelli, MA Nobrega, EM Rubin, Comparative genomics at the vertebrate extremes. Nat Rev Genet 5, 456–465 (2004). · DOI
- S Heinz, et al., Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38, 576–589 (2010). · DOI · Paper page
- E Birney, et al., Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007). · DOI · Paper page
- H Xi, et al., Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome. PLoS Genet 3, e136 (2007). · DOI
- A Visel, et al., ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457, 854–858 (2009). · DOI · Paper page
- J Xu, et al., Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells. Genes Dev 23, 2824–2838 (2009). · DOI
- K Cui, et al., Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 4, 80–93 (2009). · DOI
- F Tie, et al., CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136, 3131–3141 (2009). · DOI
- A Marson, et al., Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134, 521–533 (2008). · DOI
- X Chen, et al., Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106–1117 (2008). · DOI
- MP Creyghton, et al., H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135, 649–661 (2008). · DOI
- AC Seila, et al., Divergent transcription from active promoters. Science 322, 1849–1851 (2008). · DOI
- KS Zaret, et al., Pioneer factors, genetic competence, and inductive signaling: Programming liver and pancreas progenitors from the endoderm. Cold Spring Harb Symp Quant Biol 73, 119–126 (2008). · DOI
- ED Wederell, et al., Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing. Nucleic Acids Res 36, 4549–4564 (2008). · DOI · Paper page
- W Reith, et al., Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell 53, 897–906 (1988). · DOI
- R Dubruille, et al., Drosophila regulatory factor X is necessary for ciliated sensory neuron differentiation. Development 129, 5487–5498 (2002). · DOI
- T Perlot, FW Alt, Cis-regulatory elements and epigenetic changes control genomic rearrangements of the IgH locus. Adv Immunol 99, 1–32 (2008). · DOI
- N Maherali, et al., Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55–70 (2007).
- M Wernig, et al., In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318–324 (2007). · DOI
- L Conti, et al., Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol 3, e283 (2005). · DOI
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Self-citationVisscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425
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Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
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Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., & Amit, I. (2014) · Cell · doi:10.1016/j.cell.2014.11.018 · Cited by 2,167
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Spitz, F., & Furlong, E. E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3207 · Cited by 2,227
Kim, K. H., & Roberts, C. W. M. (2016) · Nature Medicine · doi:10.1038/nm.4036 · Cited by 1,471
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Koike, N., Yoo, S.-H., Huang, H.-C., Kumar, V., Lee, C., Kim, T.-K., & Takahashi, J. S. (2012) · Science · doi:10.1126/science.1226339 · Cited by 1,464
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307
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Shen, Y., Yue, F., McCleary, D. F., Ye, Z., Edsall, L., Kuan, S., Wagner, U., Dixon, J., Lee, L., Lobanenkov, V. V., et al. (2012) · Nature · doi:10.1038/nature11243 · Cited by 1,361
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Smallwood, S. A., Lee, H. J., Angermueller, C., Krueger, F., Saadeh, H., Peat, J., Andrews, S. R., Stegle, O., Reik, W., & Kelsey, G. (2014) · Nature Methods · doi:10.1038/nmeth.3035 · Cited by 1,125
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Jin, F., Li, Y., Dixon, J. R., Selvaraj, S., Ye, Z., Lee, A. Y., Yen, C.-A., Schmitt, A. D., Espinoza, C. A., & Ren, B. (2013) · Nature · doi:10.1038/nature12644 · Cited by 1,208
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Phillips-Cremins, J. E., Sauria, M. E. G., Sanyal, A., Gerasimova, T. I., Lajoie, B. R., Bell, J. S. K., Ong, C.-T., Hookway, T. A., Guo, C., Sun, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.053 · Cited by 1,187
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Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A. (2013) · Science · doi:10.1126/science.1232542 · Cited by 1,125
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Millán-Zambrano, G., Burton, A., Bannister, A. J., & Schneider, R. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00468-7 · Cited by 1,116
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Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
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Argelaguet, R., Arnol, D., Bredikhin, D., Deloro, Y., Velten, B., Marioni, J. C., & Stegle, O. (2020) · Genome Biology · doi:10.1186/s13059-020-02015-1 · Cited by 1,091
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Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A. Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., et al. (2013) · Nature · doi:10.1038/nature12210 · Cited by 1,049
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Heinz, S., Romanoski, C. E., Benner, C., & Glass, C. K. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3949 · Cited by 1,010
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Canver, M. C., Smith, E. C., Sher, F., Pinello, L., Sanjana, N. E., Shalem, O., Chen, D. D., Schupp, P. G., Vinjamur, D. S., Garcia, S. P., et al. (2015) · Nature · doi:10.1038/nature15521 · Cited by 886
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Ong, C.-T., & Corces, V. G. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2957 · Cited by 929
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Lara-Astiaso, D., Weiner, A., Lorenzo-Vivas, E., Zaretsky, I., Jaitin, D. A., David, E., Keren-Shaul, H., Mildner, A., Winter, D., Jung, S., et al. (2014) · Science · doi:10.1126/science.1256271 · Cited by 776
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Nott, A., Holtman, I. R., Coufal, N. G., Schlachetzki, J. C. M., Yu, M., Hu, R., Han, C. Z., Pena, M., Xiao, J., Wu, Y., et al. (2019) · Science · doi:10.1126/science.aay0793 · Cited by 699
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Pastor, W. A., Pape, U. J., Huang, Y., Henderson, H. R., Lister, R., Ko, M., McLoughlin, E. M., Brudno, Y., Mahapatra, S., Kapranov, P., et al. (2011) · Nature · doi:10.1038/nature10102 · Cited by 804
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Mansour, M. R., Abraham, B. J., Anders, L., Berezovskaya, A., Gutierrez, A., Durbin, A. D., Etchin, J., Lawton, L., Sallan, S. E., Silverman, L. B., et al. (2014) · Science · doi:10.1126/science.1259037 · Cited by 801
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Piunti, A., & Shilatifard, A. (2016) · Science · doi:10.1126/science.aad9780 · Cited by 524
Mumbach, M. R., Satpathy, A. T., Boyle, E. A., Dai, C., Gowen, B. G., Cho, S. W., Nguyen, M. L., Rubin, A. J., Granja, J. M., Kazane, K. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3963 · Cited by 490
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Shen, L., Wu, H., Diep, D., Yamaguchi, S., D’Alessio, A. C., Fung, H.-L., Zhang, K., & Zhang, Y. (2013) · Cell · doi:10.1016/j.cell.2013.04.002 · Cited by 497
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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
Seidman, J. S., Troutman, T. D., Sakai, M., Gola, A., Spann, N. J., Bennett, H., Bruni, C. M., Ouyang, Z., Li, R. Z., Sun, X., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.001 · Cited by 443
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Chen, F. X., Smith, E. R., & Shilatifard, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0010-5 · Cited by 447
Sakai, M., Troutman, T. D., Seidman, J. S., Ouyang, Z., Spann, N. J., Abe, Y., Ego, K. M., Bruni, C. M., Deng, Z., Schlachetzki, J. C. M., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.002 · Cited by 418
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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
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Raisner, R., Kharbanda, S., Jin, L., Jeng, E., Chan, E., Merchant, M., Haverty, P. M., Bainer, R., Cheung, T., Arnott, D., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.041 · Cited by 375
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Bose, D. A., Donahue, G., Reinberg, D., Shiekhattar, R., Bonasio, R., & Berger, S. L. (2017) · Cell · doi:10.1016/j.cell.2016.12.020 · Cited by 426
Spiegel, I., Mardinly, A. R., Gabel, H. W., Bazinet, J. E., Couch, C. H., Tzeng, C. P., Harmin, D. A., & Greenberg, M. E. (2014) · Cell · doi:10.1016/j.cell.2014.03.058 · Cited by 416
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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
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Dorighi, K. M., Swigut, T., Henriques, T., Bhanu, N. V., Scruggs, B. S., Nady, N., Still, C. D., Garcia, B. A., Adelman, K., & Wysocka, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.018 · Cited by 403
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Tyssowski, K. M., DeStefino, N. R., Cho, J.-H., Dunn, C. J., Poston, R. G., Carty, C. E., Jones, R. D., Chang, S. M., Romeo, P., Wurzelmann, M. K., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.04.001 · Cited by 390
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Hay, D., Hughes, J. R., Babbs, C., Davies, J. O. J., Graham, B. J., Hanssen, L. L. P., Kassouf, M. T., Oudelaar, A. M., Sharpe, J. A., Suciu, M. C., et al. (2016) · Nature Genetics · doi:10.1038/ng.3605 · Cited by 385
Nativio, R., Lan, Y., Donahue, G., Sidoli, S., Berson, A., Srinivasan, A. R., Shcherbakova, O., Amlie-Wolf, A., Nie, J., Cui, X., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0696-0 · Cited by 380
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Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D. (2013) · Cell · doi:10.1016/j.cell.2013.03.011 · Cited by 365
Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single Cells
Xie, S., Duan, J., Li, B., Zhou, P., & Hon, G. C. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.03.007 · Cited by 334
Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples
Jin, W., Tang, Q., Wan, M., Cui, K., Zhang, Y., Ren, G., Ni, B., Sklar, J., Przytycka, T. M., Childs, R., et al. (2015) · Nature · doi:10.1038/nature15740 · Cited by 332
Oishi, Y., Spann, N. J., Link, V. M., Muse, E. D., Strid, T., Edillor, C., Kolar, M. J., Matsuzaka, T., Hayakawa, S., Tao, J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.11.009 · Cited by 342
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
Rubin, A. J., Barajas, B. C., Furlan-Magaril, M., Lopez-Pajares, V., Mumbach, M. R., Howard, I., Kim, D. S., Boxer, L. D., Cairns, J., Spivakov, M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3935 · Cited by 293
Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.003 · Cited by 320
In situ fixation redefines quiescence and early activation of skeletal muscle stem cells
Machado, L., Esteves de Lima, J., Fabre, O., Proux, C., Legendre, R., Szegedi, A., Varet, H., Ingerslev, L. R., Barrès, R., Relaix, F., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.080 · Cited by 328
Takeda, D. Y., Spisák, S., Seo, J.-H., Bell, C., O’Connor, E., Korthauer, K., Ribli, D., Csabai, I., Solymosi, N., Szállási, Z., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.037 · Cited by 317
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
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
Emerging roles for chromatin as a signal integration and storage platform
Badeaux, A. I., & Shi, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3545 · Cited by 291
Effect of natural genetic variation on enhancer selection and function
Heinz, S., Romanoski, C. E., Benner, C., Allison, K. A., Kaikkonen, M. U., Orozco, L. D., & Glass, C. K. (2013) · Nature · doi:10.1038/nature12615 · Cited by 298
Epigenetic patterns in a complete human genome
Gershman, A., Sauria, M. E. G., Guitart, X., Vollger, M. R., Hook, P. W., Hoyt, S. J., Jain, M., Shumate, A., Razaghi, R., Koren, S., et al. (2022) · Science · doi:10.1126/science.abj5089 · Cited by 297
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
Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells
Soucie, E. L., Weng, Z., Geirsdóttir, L., Molawi, K., Maurizio, J., Fenouil, R., Mossadegh-Keller, N., Gimenez, G., VanHille, L., Beniazza, M., et al. (2016) · Science · doi:10.1126/science.aad5510 · Cited by 263
Li, M., He, Y., Dubois, W., Wu, X., Shi, J., & Huang, J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.020 · Cited by 264
Decoding enhancers using massively parallel reporter assays
Inoue, F., & Ahituv, N. (2015) · Genomics · doi:10.1016/j.ygeno.2015.06.005 · Cited by 272
Intragenic Enhancers Act as Alternative Promoters
Kowalczyk, M. S., Hughes, J. R., Garrick, D., Lynch, M. D., Sharpe, J. A., Sloane-Stanley, J. A., McGowan, S. J., De Gobbi, M., Hosseini, M., Vernimmen, D., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.021 · Cited by 267
AP-1 imprints a reversible transcriptional programme of senescent cells.
Martínez-Zamudio, R. I., Roux, P.-F., de Freitas, J. A. N. L. F., Robinson, L., Doré, G., Sun, B., Belenki, D., Milanovic, M., Herbig, U., Schmitt, C. A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0529-5 · Cited by 236
NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers
Wang, H., Zang, C., Taing, L., Arnett, K. L., Wong, Y. J., Pear, W. S., Blacklow, S. C., Liu, X. S., & Aster, J. C. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315023111 · Cited by 252
Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity
Kim, T.-H., Li, F., Ferreiro-Neira, I., Ho, L.-L., Luyten, A., Nalapareddy, K., Long, H., Verzi, M., & Shivdasani, R. A. (2014) · Nature · doi:10.1038/nature12903 · Cited by 257
Chepelev, I., Wei, G., Wangsa, D., Tang, Q., & Zhao, K. (2012) · Cell Research · doi:10.1038/cr.2012.15 · Cited by 253
Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries
Sun, J. H., Zhou, L., Emerson, D. J., Phyo, S. A., Titus, K. R., Gong, W., Gilgenast, T. G., Beagan, J. A., Davidson, B. L., Tassone, F., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.005 · Cited by 249
“Finally, to better understand how the FXS topological changes might be connected to FMR1 trancriptional silencing, we mined published ChIP-seq data in GM12878 cells for H3K27ac, an established mark of active enhancers (Creyghton et al., 2010).”
MethodKim, C. G., Jang, M., Kim, Y., Leem, G., Kim, K. H., Lee, H., Kim, T.-S., Choi, S. J., Kim, H.-D., Han, J. W., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay0555 · Cited by 245
Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation
Siersbæk, R., Madsen, J. G. S., Javierre, B. M., Nielsen, R., Bagge, E. K., Cairns, J., Wingett, S. W., Traynor, S., Spivakov, M., Fraser, P., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.010 · Cited by 243
Cell-of-origin-specific 3D genome structure acquired during somatic cell reprogramming
Krijger, P. H. L., Di Stefano, B., de Wit, E., Limone, F., van Oevelen, C., de Laat, W., & Graf, T. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.01.007 · Cited by 217
Houtepen, L. C., Vinkers, C. H., Carrillo-Roa, T., Hiemstra, M., van Lier, P. A., Meeus, W., Branje, S., Heim, C. M., Nemeroff, C. B., Mill, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10967 · Cited by 242
Self-citationCruz-Molina, S., Respuela, P., Tebartz, C., Kolovos, P., Nikolic, M., Fueyo, R., van Ijcken, W. F. J., Grosveld, F., Frommolt, P., Bazzi, H., et al. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.02.004 · Cited by 240
Histone H3 globular domain acetylation identifies a new class of enhancers
Pradeepa, M. M., Grimes, G. R., Kumar, Y., Olley, G., Taylor, G. C. A., Schneider, R., & Bickmore, W. A. (2016) · Nature Genetics · doi:10.1038/ng.3550 · Cited by 240
Genome-wide mapping of global-to-local genetic effects on human facial shape
Claes, P., Roosenboom, J., White, J. D., Swigut, T., Sero, D., Li, J., Lee, M. K., Zaidi, A., Mattern, B. C., Liebowitz, C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0057-4 · Cited by 235
Transcription Factor Cooperativity in Early Adipogenic Hotspots and Super-Enhancers
Siersbæk, R., Rabiee, A., Nielsen, R., Sidoli, S., Traynor, S., Loft, A., Poulsen, L. L. C., Rogowska-Wrzesinska, A., Jensen, O. N., & Mandrup, S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.042 · Cited by 234
Marzi, S. J., Leung, S. K., Ribarska, T., Hannon, E., Smith, A. R., Pishva, E., Poschmann, J., Moore, K., Troakes, C., Al-Sarraj, S., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0253-7 · Cited by 232
Molecular components of the circadian clock in mammals
Takahashi, J. S. (2015) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12514 · Cited by 230
Rewiring of human neurodevelopmental gene regulatory programs by human accelerated regions
Girskis, K. M., Stergachis, A. B., DeGennaro, E. M., Doan, R. N., Qian, X., Johnson, M. B., Wang, P. P., Sejourne, G. M., Nagy, M. A., Pollina, E. A., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.08.005 · Cited by 193
Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates
Wang, W., Hu, C.-K., Zeng, A., Alegre, D., Hu, D., Gotting, K., Ortega Granillo, A., Wang, Y., Robb, S., Schnittker, R., et al. (2020) · Science · doi:10.1126/science.aaz3090 · Cited by 210
Link, V. M., Duttke, S. H., Chun, H. B., Holtman, I. R., Westin, E., Hoeksema, M. A., Abe, Y., Skola, D., Romanoski, C. E., Tao, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.04.018 · Cited by 182
Avrahami, D., Li, C., Zhang, J., Schug, J., Avrahami, R., Rao, S., Stadler, M. B., Burger, L., Schübeler, D., Glaser, B., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.025 · Cited by 207
Spatially resolved epigenomic profiling of single cells in complex tissues
Lu, T., Ang, C. E., & Zhuang, X. (2022) · Cell · doi:10.1016/j.cell.2022.09.035 · Cited by 197
Wes, P. D., Holtman, I. R., Boddeke, E. W. G. M., Möller, T., & Eggen, B. J. L. (2016) · Glia · doi:10.1002/glia.22866 · Cited by 167
Zawistowski, J. S., Bevill, S. M., Goulet, D. R., Stuhlmiller, T. J., Beltran, A. S., Olivares-Quintero, J. F., Singh, D., Sciaky, N., Parker, J. S., Rashid, N. U., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0653 · Cited by 180
Neri, F., Incarnato, D., Krepelova, A., Rapelli, S., Pagnani, A., Zecchina, R., Parlato, C., & Oliviero, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-8-r91 · Cited by 179
Suppression of Enhancer Overactivation by a RACK7-Histone Demethylase Complex
Shen, H., Xu, W., Guo, R., Rong, B., Gu, L., Wang, Z., He, C., Zheng, L., Hu, X., Hu, Z., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.064 · Cited by 184
Léveillé, N., Melo, C. A., Rooijers, K., Díaz-Lagares, A., Melo, S. A., Korkmaz, G., Lopes, R., Moqadam, F. A., Maia, A. R., Wijchers, P. J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7520 · Cited by 183
DNA methylation in lung cells is associated with asthma endotypes and genetic risk
Nicodemus-Johnson, J., Myers, R. A., Sakabe, N. J., Sobreira, D. R., Hogarth, D. K., Naureckas, E. T., Sperling, A. I., Solway, J., White, S. R., Nobrega, M. A., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.90151 · Cited by 180
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers
Murakami, K., Günesdogan, U., Zylicz, J. J., Tang, W. W. C., Sengupta, R., Kobayashi, T., Kim, S., Butler, R., Dietmann, S., & Azim Surani, M. (2016) · Nature · doi:10.1038/nature16480 · Cited by 180
Metadata
- Authors
- Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., Boyer, L. A., Young, R. A., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Jaenisch, Rudolf
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-24
- Volume
- 107
- Issue
- 50
- Pages
- 21931-21936
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3003124
- OpenAlex
- W1981030303
- Cited by
- 4,302
- References
- 9
- Citations by year
- 2026: 228 · 2025: 286 · 2024: 349 · 2023: 365 · 2022: 345 · 2021: 362 · 2020: 346 · 2019: 315 · 2018: 292 · 2017: 267 · 2016: 261 · 2015: 242 · 2014: 239 · 2013: 220 · 2012: 124
- FWCI
- 51.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (2r01ca084198-10)
- U.S. Public Health Service (5-RO1-HDO45022)
- National Human Genome Research Institute (HG002668, R01HG002668)
- National Cancer Institute (R01-CA084198, R01CA087869, 5-RO1-CA87869, P01CA042063, R37CA084198, P30CA014051, P30-CA-14051, P01 CA 42063)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD045022)
- 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
- enhancer activity, poised enhancers, H3K4me1, developmental state, embryonic stem cells, nuclear reprogramming, cell differentiation, chromatin regulation, mouse tissues
- MeSH terms
- Acetylation, Animals, Cell Differentiation, Cell Line, Enhancer Elements, Genetic, Histones, Mice, Inbred C57BL, Gene Expression Regulation, Developmental, Mice
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