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The accessible chromatin landscape of the human genome
Open accessAbstract
DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation. An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. This paper describes the first extensive map of human DNaseI hypersensitive sites — markers of regulatory DNA — in 125 diverse cell and tissue types. Integration of this information with other data sets generated by ENCODE (Encyclopedia of DNA Elements) identified new relationships between chromatin accessibility, transcription, DNA methylation and regulatory-factor occupancy patterns. Evolutionary-conservation analysis revealed signatures of recent functional constraint within DNaseI hypersensitive sites.
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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 [40]
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“According to recent estimates, the number of enhancers in the human genome ranges from 400,000 to 1,000,000 [22,23].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [23]
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“To some degree this can be overcome by correlative approaches (e.g. correlating open chromatin status between promoters and enhancers across large numbers of cell types) but such links remain inferential45,134,135.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [45]
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“most genetic variation that contributes to common psychiatric disorders is not in protein-coding regions”
From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Thurman et al., 2012
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“Thus, methods that measure chromatin accessibility by combining sensitivity to enzymatic digestion with sequencing6–8 provide an integrated map of chromatin states that encompasses a diverse repertoire of functional regulatory elements2,5.”
From Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility (2019) · cites this paper as [2]
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“Both classical observations5 and recent genome-wide efforts2 have shown that active regulatory elements are canonically nucleosome free and accessible to transcriptional machinery.”
From Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility (2019) · cites this paper as [2]
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“We found that chromatin accessibility from bulk ATAC-seq8 and DNase-seq2 and the aggregate chromatin accessibility across the different single-cell technologies18,19,24,25 were highly correlated (Fig. 1c,d).”
From Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility (2019) · cites this paper as [2]
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Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Self-citationLandscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187
Self-citationGENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585
miRBase: tools for microRNA genomics
Griffiths‐Jones, S., Saini, H. K., van Dongen, S., & Enright, A. J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm952 · Cited by 4,432
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
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
Self-citationThe long-range interaction landscape of gene promoters
Sanyal, A., Lajoie, B. R., Jain, G., & Dekker, J. (2012) · Nature · doi:10.1038/nature11279 · Cited by 1,489
Self-citationHigh-Resolution Mapping and Characterization of Open Chromatin across the Genome
Boyle, A. P., Davis, S., Shulha, H. P., Meltzer, P., Margulies, E. H., Weng, Z., Furey, T. S., & Crawford, G. E. (2008) · Cell · doi:10.1016/j.cell.2007.12.014 · Cited by 1,415
Self-citationDNA-binding factors shape the mouse methylome at distal regulatory regions
Stadler, M. B., Murr, R., Burger, L., Ivanek, R., Lienert, F., Schöler, A., Nimwegen, E. V., Wirbelauer, C., Oakeley, E. J., Gaidatzis, D., et al. (2011) · Nature · doi:10.1038/nature10716 · Cited by 1,383
An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells
Kim, J., Chu, J., Shen, X., Wang, J., & Orkin, S. H. (2008) · Cell · doi:10.1016/j.cell.2008.02.039 · Cited by 1,361
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Gate, R. E., Cheng, C. S., Aiden, A. P., Siba, A., Tabaka, M., Lituiev, D., Machol, I., Gordon, M. G., Subramaniam, M., Shamim, M., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0156-2 · Cited by 181
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Angeloni, A., & Bogdanović, O. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190030 · Cited by 181
Wang, K., & Chang, H. Y. (2018) · Circulation Research · doi:10.1161/circresaha.118.310998 · Cited by 180
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Thompson, D. A., Regev, A., & Roy, S. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-012908 · Cited by 178
In search of the determinants of enhancer–promoter interaction specificity
van Arensbergen, J., van Steensel, B., & Bussemaker, H. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.004 · Cited by 180
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Smith, M. A., Gesell, T., Stadler, P. F., & Mattick, J. S. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt596 · Cited by 178
Chiou, J., Zeng, C., Zhang, C., Han, J. Y., Schlichting, M., Miller, M., Mendez, R., Huang, S., Wang, J., Sui, Y., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00823-0 · Cited by 186
Farr, S. E., Woods, E. J., Joseph, J. A., Garaizar, A., & Collepardo‐Guevara, R. (2021) · Nature Communications · doi:10.1038/s41467-021-23090-3 · Cited by 178
Navigating the transcriptional roadmap regulating plant secondary cell wall deposition
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Landscape of allele-specific transcription factor binding in the human genome
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Wong, E. S., Zheng, D., Tan, S. Z., Bower, N. I., Garside, V., Vanwalleghem, G., Gaiti, F., Scott, E., Hogan, B. M., Kikuchi, K., et al. (2020) · Science · doi:10.1126/science.aax8137 · Cited by 176
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Reilly, M. T., Faulkner, G. J., Dubnau, J., Ponomarev, I., & Gage, F. H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3369-13.2013 · Cited by 175
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Duttke, S. H. C., Chang, M. W., Heinz, S., & Benner, C. W. (2019) · Genome Research · doi:10.1101/gr.253492.119 · Cited by 180
Tobi, E. W., Slieker, R. C., Stein, A. D., Suchiman, H. E. D., Slagboom, P. E., van Zwet, E. W., Heijmans, B. T., & Lumey, L. H. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv043 · Cited by 173
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Link, A., Balaguer, F., Shen, Y., Lozano, J. J., Leung, H. E., Boland, C. R., & Goel, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057709 · Cited by 172
Nuclear stability and transcriptional directionality separate functionally distinct RNA species
Andersson, R., Refsing Andersen, P., Valen, E., Core, L. J., Bornholdt, J., Boyd, M., Heick Jensen, T., & Sandelin, A. (2014) · Nature Communications · doi:10.1038/ncomms6336 · Cited by 171
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Liu, G., Mattick, J. S., & Taft, R. J. (2013) · Cell Cycle · doi:10.4161/cc.25134 · Cited by 171
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Lio, C.-W., Zhang, J., González-Avalos, E., Hogan, P. G., Chang, X., & Rao, A. (2016) · eLife · doi:10.7554/elife.18290 · Cited by 170
Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum
Frank, C. L., Liu, F., Wijayatunge, R., Song, L., Biegler, M. T., Yang, M. G., Vockley, C. M., Safi, A., Gersbach, C. A., Crawford, G. E., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3995 · Cited by 170
Self-citationTransformers and genome language models
Consens, M. E., Dufault, C., Wainberg, M., Forster, D., Karimzadeh, M., Goodarzi, H., Theis, F. J., Moses, A. M., & Wang, B. (2025) · Nature Machine Intelligence · doi:10.1038/s42256-025-01007-9 · Cited by 170
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Ludwig, L. S., Lareau, C. A., Bao, E. L., Nandakumar, S. K., Muus, C., Ulirsch, J. C., Chowdhary, K., Buenrostro, J. D., Mohandas, N., An, X., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.046 · Cited by 167
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Ing-Simmons, E., Seitan, V. C., Faure, A. J., Flicek, P., Carroll, T., Dekker, J., Fisher, A. G., Lenhard, B., & Merkenschlager, M. (2015) · Genome Research · doi:10.1101/gr.184986.114 · Cited by 167
Self-citationEvaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia
Bryois, J., Garrett, M. E., Song, L., Safi, A., Giusti-Rodriguez, P., Johnson, G. D., Shieh, A. W., Buil, A., Fullard, J. F., Roussos, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05379-y · Cited by 167
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Liu, X., Homma, A., Sayadi, J., Yang, S., Ohashi, J., & Takumi, T. (2016) · Scientific Reports · doi:10.1038/srep19675 · Cited by 166
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Donaghey, J., Thakurela, S., Charlton, J., Chen, J., Smith, Z. D., Gu, H., Pop, R., Clement, K., Stamenova, E. K., Karnik, R., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0034-3 · Cited by 166
Local Determinants of the Mutational Landscape of the Human Genome
González-Pérez, A., Sabarinathan, R., & López-Bigas, N. (2019) · Cell · doi:10.1016/j.cell.2019.02.051 · Cited by 172
Grossman, S. R., Zhang, X., Wang, L., Engreitz, J., Melnikov, A., Rogov, P., Tewhey, R., Isakova, A., Deplancke, B., Bernstein, B. E., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621150114 · Cited by 165
Harnessing the potential of epigenetic therapy to target solid tumors
Ahuja, N., Easwaran, H., & Baylin, S. B. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69736 · Cited by 165
Gussow, A. B., Copeland, B. R., Dhindsa, R. S., Wang, Q., Petrovski, S., Majoros, W. H., Allen, A. S., & Goldstein, D. B. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181604 · Cited by 165
Davie, K., Jacobs, J., Atkins, M., Potier, D., Christiaens, V., Halder, G. A., & Aerts, S. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004994 · Cited by 164
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Nguyen, T. C., Cao, X., Yu, P., Shu Dong, X. I. A. O., Lu, J., Biase, F. H., Sridhar, B., Huang, N., Zhang, K., & Zhong, S. (2016) · Nature Communications · doi:10.1038/ncomms12023 · Cited by 164
EnhancerAtlas: a resource for enhancer annotation and analysis in 105 human cell/tissue types
Gao, T., He, B., Liu, S., Zhu, H., Tan, K., & Qian, J. X. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw495 · Cited by 164
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Yan, J., Qiu, Y., dos Santos, A. M. R., Yin, Y., Li, Y. E., Vinckier, N., Nariai, N., Benaglio, P., Raman, A., Li, X., et al. (2021) · Nature · doi:10.1038/s41586-021-03211-0 · Cited by 163
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Wang, Y., Yuan, P., Yan, Z., Yang, M., Huo, Y., Nie, Y., Zhu, X., Qiao, J., & Yan, L. (2021) · Nature Communications · doi:10.1038/s41467-021-21409-8 · Cited by 163
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Ernst, J., Melnikov, A., Zhang, X., Wang, L., Rogov, P., Mikkelsen, T. S., & Kellis, M. (2016) · Nature Biotechnology · doi:10.1038/nbt.3678 · Cited by 162
Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes
Blattler, A., Yao, L., Witt, H. N., Guo, Y., Nicolet, C. M., Berman, B. P., & Farnham, P. (2014) · Genome biology · doi:10.1186/s13059-014-0469-0 · Cited by 162
Quilez, J., Guilmatre, A., Garg, P., Highnam, G., Gymrek, M., Erlich, Y., Joshi, R. S., Mittelman, D., & Sharp, A. J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw219 · Cited by 164
Multi-species annotation of transcriptome and chromatin structure in domesticated animals
Foissac, S., Djebali, S., Munyard, K., Vialaneix, N., Rau, A., Muret, K., Esquerré, D., Zytnicki, M., Derrien, T., Bardou, P., et al. (2019) · BMC Biology · doi:10.1186/s12915-019-0726-5 · Cited by 162
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Sung, M., Guertin, M. J., Baek, S., & Hager, G. L. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.016 · Cited by 160
Lu, X., Peloso, G. M., Liu, D. J., Wu, Y., Zhang, H., Zhou, W., Li, J., Tang, C. S.-M., Dorajoo, R., Li, H., et al. (2017) · Nature Genetics · doi:10.1038/ng.3978 · Cited by 160
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Bell, C. G., Gao, F., Yuan, W., Roos, L., Acton, R., Xia, Y., Bell, J. T., Ward, K. J., Mangino, M., Hysi, P. G., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01586-1 · Cited by 157
Integrating Diverse Datasets Improves Developmental Enhancer Prediction
Erwin, G. D., Oksenberg, N., Truty, R., Kostka, D., Murphy, K. K., Ahituv, N., Pollard, K. S., & Capra, J. A. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003677 · Cited by 156
An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging
Yuan, T., Jiao, Y., de Jong, S., Ophoff, R. A., Beck, S., & Teschendorff, A. E. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1004996 · Cited by 155
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Vernimmen, D., & Bickmore, W. A. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.10.004 · Cited by 155
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Smallwood, A., & Ren, B. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.02.005 · Cited by 155
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Richart, L., Pau, E. C. D. S., Rio‐Machín, A., de Andrés, M. P., Cigudosa, J. C., Lobo, V. J. S.-A., & Real, F. X. (2016) · Nature Communications · doi:10.1038/ncomms10153 · Cited by 155
Schmidt, E. M., Zhang, J., Zhou, W., Chen, J., Mohlke, K. L., Chen, Y., & Willer, C. J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv201 · Cited by 152
Gothe, H. J., Bouwman, B. A. M., Gusmao, E. G., Piccinno, R., Petrosino, G., Sayols, S., Drechsel, O., Minneker, V., Josipović, N., Mizi, A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.015 · Cited by 152
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Gschwind, A. R., Mualim, K. S., Karbalayghareh, A., Sheth, M. U., Dey, K. K., Jagoda, E., Nurtdinov, R., Xi, W., Tan, A. S., Galante, J., et al. (2026) · Nature · doi:10.1038/s41586-026-10781-4 · Cited by 161
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Ooi, W. F., Xing, M., Xu, C., Yao, X., Ramlee, M. K., Lim, M. C., Cao, F., Lim, K. J., Babu, D., Poon, L.-F., et al. (2016) · Nature Communications · doi:10.1038/ncomms12983 · Cited by 150
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Wang, Q., Xiong, F., Wu, G., Liu, W., Chen, J., Wang, B., & Chen, Y. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01382-9 · Cited by 150
Dror, I., Golan, T., Levy, C., Rohs, R., & Mandel‐Gutfreund, Y. (2015) · Genome Research · doi:10.1101/gr.184671.114 · Cited by 149
Carter, B., Ku, W. L., Kang, J. Y., Hu, G., Perrie, J., Tang, Q., & Zhao, K. (2019) · Nature Communications · doi:10.1038/s41467-019-11559-1 · Cited by 148
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Oh, K., Patel, H., Gottschalk, R. A., Lee, W. S., Baek, S., Fraser, I. D. C., Hager, G. L., & Sung, M. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.012 · Cited by 148
Beytebiere, J. R., Trott, A. J., Greenwell, B. J., Osborne, C. A., Vitet, H., Spence, J., Yoo, S. H., Chen, Z., Takahashi, J. S., Ghaffari, N., et al. (2019) · Genes & Development · doi:10.1101/gad.322198.118 · Cited by 152
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Liang, L., Cao, C., Ji, L., Cai, Z., Wang, D., Ye, R., Chen, J., Yu, X., Zhou, J., Bai, Z., et al. (2023) · Nature · doi:10.1038/s41586-023-06323-x · Cited by 147
Massively parallel characterization of transcriptional regulatory elements
Agarwal, V., Inoue, F., Schubach, M., Penzar, D., Martin, B. K., Dash, P. M., Keukeleire, P., Zhang, Z., Sohota, A., Zhao, J., et al. (2025) · Nature · doi:10.1038/s41586-024-08430-9 · Cited by 146
Self-citationHuman Promoters Are Intrinsically Directional
Duttke, S. H. C., Lacadie, S. A., Ibrahim, M. M., Glass, C. K., Corcoran, D. L., Benner, C. W., Heinz, S., Kadonaga, J. T., & Ohler, U. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.12.029 · Cited by 145
Yáñez-Cuna, J. O., Arnold, C. D., Stampfel, G., Boryń, Ł. M., Gerlach, D., Rath, M., & Stark, A. (2014) · Genome Research · doi:10.1101/gr.169243.113 · Cited by 145
Li, J., Shou, J., Guo, Y., Tang, Y., Wu, Y., Jia, Z., Zhai, Y., Chen, Z., Xu, Q., & Wu, Q. (2015) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjv016 · Cited by 144
Plant Enhancers: A Call for Discovery
Weber, B., Zicola, J., Oka, R., & Stam, M. E. (2016) · Trends in Plant Science · doi:10.1016/j.tplants.2016.07.013 · Cited by 144
High-throughput chromatin accessibility profiling at single-cell resolution
Mezger, A., Klemm, S. L., Mann, I. K., Brower, K. K., Mir, A. A., Bostick, M. L., Farmer, A. A., Fordyce, P. M., Linnarsson, S., & Greenleaf, W. J. (2018) · Nature Communications · doi:10.1038/s41467-018-05887-x · Cited by 144
Constructing 3D interaction maps from 1D epigenomes
Zhu, Y., Chen, Z., Zhang, K., Wang, M., Medovoy, D., Whitaker, J. W., Ding, B., Li, N., Zheng, L., & Wang, W. (2016) · Nature Communications · doi:10.1038/ncomms10812 · Cited by 146
Transcription Factors and DNA Play Hide and Seek
Suter, D. M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.03.003 · Cited by 143
Camp, J. G., Frank, C. L., Lickwar, C. R., Guturu, H., Rube, T., Wenger, A. M., Chen, J., Bejerano, G., Crawford, G. E., & Rawls, J. F. (2014) · Genome Research · doi:10.1101/gr.165845.113 · Cited by 143
Self-citationMachine-guided design of cell-type-targeting cis-regulatory elements
Gosai, S. J., Castro, R. I., Fuentes, N., Butts, J. C., Mouri, K., Alasoadura, M., Kales, S., Nguyen, T. T. L., Noche, R. R., Rao, A. S., et al. (2024) · Nature · doi:10.1038/s41586-024-08070-z · Cited by 142
Timofeeva, O. A., Tarasova, N. I., Zhang, X., Chasovskikh, S., Cheema, A. K., Wang, H., Brown, M. L., & Dritschilo, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211805110 · Cited by 142
Self-citationPioneer Factor-Nucleosome Binding Events during Differentiation Are Motif Encoded
Meers, M. P., Janssens, D. H., & Henikoff, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.025 · Cited by 142
Morikawa, H., Ohkura, N., Vandenbon, A., Itoh, M., Nagao-Sato, S., Kawaji, H., Lassmann, T., Carninci, P., Hayashizaki, Y., Forrest, A. R. R., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312717110 · Cited by 140
Sugathan, A., & Waxman, D. J. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00280-13 · Cited by 140
Outchkourov, N. S., Muiño, J. M., Kaufmann, K., van IJcken, W. F. J., Koerkamp, M. J. A. G., van Leenen, D., de Graaf, P., Holstege, F. C. P., Grosveld, F. G., & Timmers, H. T. M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.02.030 · Cited by 139
Gross, T. J., Kremens, K., Powers, L. S., Brink, B., Knutson, T. M., Domann, F. E., Philibert, R. A., Milhem, M. M., & Monick, M. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301758 · Cited by 139
Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
Shi, J., Marconett, C. N., Duan, J., Hyland, P. L., Li, P., Wang, Z., Wheeler, W., Zhou, B., Campan, M., Lee, D. S., et al. (2014) · Nature Communications · doi:10.1038/ncomms4365 · Cited by 137
Laminopathies disrupt epigenomic developmental programs and cell fate
Perovanović, J., Dell’Orso, S., Gnocchi, V. F., Jaiswal, J. K., Sartorelli, V., Vigouroux, C., Mamchaoui, K., Mouly, V., Bonne, G., & Hoffman, E. P. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad4991 · Cited by 137
Genomic insights into cancer-associated aberrant CpG island hypermethylation
Sproul, D., & Meehan, R. R. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/els063 · Cited by 135
Sijacic, P., Bajic, M., McKinney, E. C., Meagher, R. B., & Deal, R. B. (2018) · The Plant Journal · doi:10.1111/tpj.13882 · Cited by 135
Pioneer factors: roles and their regulation in development
Barral, A., & Zaret, K. S. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.10.007 · Cited by 135
Patten, D. K., Corleone, G., Győrffy, B., Perone, Y., Slaven, N., Barozzi, I., Erdős, E., Saiakhova, A., Goddard, K. S., Vingiani, A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0091-x · Cited by 134
Rodin, R. E., Dou, Y., Kwon, M., Sherman, M. A., D’Gama, A. M., Doan, R. N., Rento, L. M., Girskis, K. M., Bohrson, C. L., Kim, S. N., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00765-6 · Cited by 135
Cardiac cell type–specific gene regulatory programs and disease risk association
Hocker, J. D., Poirion, O., Zhu, F., Buchanan, J., Zhang, K., Chiou, J., Wang, T., Zhang, Q., Hou, X., Li, Y. E., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf1444 · Cited by 136
Liu, Q., Jiang, C., Xu, J., Zhao, M., Bortle, K. V., Cheng, X., Wang, G., Chang, H. Y., Wu, J. C., & Snyder, M. P. (2017) · Circulation Research · doi:10.1161/circresaha.116.310456 · Cited by 134
scBasset: sequence-based modeling of single-cell ATAC-seq using convolutional neural networks
Yuan, H., & Kelley, D. R. (2022) · Nature Methods · doi:10.1038/s41592-022-01562-8 · Cited by 133
Jung‐Klawitter, S., Fuchs, N. V., Upton, K. R., Muñoz-López, M., Shukla, R., Wang, J., García-Cañadas, M., Lopez‐Ruiz, C., Gerhardt, D. J., Sebe, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms10286 · Cited by 131
Metadata
- Authors
- Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., Garg, K., John, S., Sandstrom, R., Bates, D., Boatman, L., Canfield, T. K., Diegel, M., Dunn, D., Ebersol, A. K., Frum, T., Giste, E., Johnson, A. K., Johnson, E. M., Kutyavin, T., Lajoie, B., Lee, B.-K., Lee, K., London, D., Lotakis, D., Neph, S., Neri, F., Nguyen, E. D., Qu, H., Reynolds, A. P., Roach, V., Safi, A., Sanchez, M. E., Sanyal, A., Shafer, A., Simon, J. M., Song, L., Vong, S., Weaver, M., Yan, Y., Zhang, Z., Zhang, Z., Lenhard, B., Tewari, M., Dorschner, M. O., Hansen, R. S., Navas, P. A., Stamatoyannopoulos, G., Iyer, V. R., Lieb, J. D., Sunyaev, S. R., Akey, J. M., Sabo, P. J., Kaul, R., Furey, T. S., Dekker, J., Crawford, G. E., & Stamatoyannopoulos, J. A.
- Affiliations
- University of Washington (US)
- Duke University (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- University of Massachusetts Chan Medical School (US)
- The University of Texas at Austin (US)
- Chinese Academy of Sciences (CN)
- University of North Carolina at Chapel Hill (US)
- University of Bergen (NO)
- Brigham and Women's Hospital (US)
- Corresponding author
- Stamatoyannopoulos, John A.
- ORCID
- Rynes, Eric
- Vierstra, Jeff
- Maurano, Matthew T.
- Haugen, Eric
- Sheffield, Nathan C.
- Stergachis, Andrew B.
- Vernot, Benjamin
- Garg, Kavita
- Sandstrom, Richard
- Bates, Daniel
- Frum, Tristan
- Lajoie, Bryan
- Lee, Bum-Kyu
- Lee, Kristen
- Lotakis, Dimitra
- Neph, Shane
- Qu, Hongzhu
- Reynolds, Alex P.
- Safi, Alexias
- Sanyal, Amartya
- Simon, Jeremy M.
- Song, Lingyun
- Zhang, Zhancheng
- Zhang, Zhuzhu
- Lenhard, Boris
- Tewari, Muneesh
- Iyer, Vishwanath R.
- Sunyaev, Shamil R.
- Akey, Joshua M.
- Sabo, Peter J.
- Kaul, Rajinder
- Furey, Terrence S.
- Dekker, Job
- Crawford, Gregory E.
- Stamatoyannopoulos, John A.
- Venue
- Nature
- Published
- 2012-09
- Volume
- 489
- Issue
- 7414
- Pages
- 75-82
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3721348
- OpenAlex
- W1964963969
- Cited by
- 2,679
- References
- 38
- Citations by year
- 2026: 81 · 2025: 97 · 2024: 119 · 2023: 140 · 2022: 170 · 2021: 218 · 2020: 192 · 2019: 199 · 2018: 227 · 2017: 238 · 2016: 238 · 2015: 247 · 2014: 242 · 2013: 235 · 2012: 31
- FWCI
- 96.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- UNC Libraries
- Funders
- National Science Foundation (HHSN261200800001E, DGE-0-718124, 0718124)
- Norges Forskningsråd
- National Institutes of Health (#HHSN261200800001E, 5u54hg004563-04, HG004563)
- National Institute of Mental Health (R01MH084676)
- National Human Genome Research Institute (U54‑HG004563, U54HG004592, HG004592, HG004563, R01HG003143)
- National Cancer Institute (HHSN261200800001E), P30CA016086)
- National Institute of General Medical Sciences (R01GM076036, GM076036)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK095678)
- 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
- DNase I hypersensitive sites, chromatin accessibility, cis-regulatory elements, enhancers, promoter, insulators, silencers, locus control region, cell type-specific gene regulation, DNA methylation, transcription factor occupancy, evolutionary constraints, mutation rate, pluripotent cells, human diversity, ENCODE
- MeSH terms
- Chromatin, Deoxyribonuclease I, DNA, DNA-Binding Proteins, Encyclopedias as Topic, Humans, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Genome, Human, DNA Footprinting, Evolution, Molecular, DNA Methylation, Genomics, Transcription Initiation Site, Molecular Sequence Annotation, Mutation Rate
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