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The accessible chromatin landscape of the human genome.

Publication ,  Journal Article
Thurman, RE; Rynes, E; Humbert, R; Vierstra, J; Maurano, MT; Haugen, E; Sheffield, NC; Stergachis, AB; Wang, H; Vernot, B; Garg, K; John, S ...
Published in: Nature
September 6, 2012

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

75 / 82

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Mutation Rate
  • Molecular Sequence Annotation
  • Humans
  • Genomics
  • Genome, Human
 

Citation

APA
Chicago
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Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., … Stamatoyannopoulos, J. A. (2012). The accessible chromatin landscape of the human genome. Nature, 489(7414), 75–82. https://doi.org/10.1038/nature11232
Thurman, Robert E., Eric Rynes, Richard Humbert, Jeff Vierstra, Matthew T. Maurano, Eric Haugen, Nathan C. Sheffield, et al. “The accessible chromatin landscape of the human genome.Nature 489, no. 7414 (September 6, 2012): 75–82. https://doi.org/10.1038/nature11232.
Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, et al. The accessible chromatin landscape of the human genome. Nature. 2012 Sep 6;489(7414):75–82.
Thurman, Robert E., et al. “The accessible chromatin landscape of the human genome.Nature, vol. 489, no. 7414, Sept. 2012, pp. 75–82. Pubmed, doi:10.1038/nature11232.
Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, John S, Sandstrom R, Bates D, Boatman L, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee B-K, Lee K, London D, Lotakis D, Neph S, Neri F, Nguyen ED, Qu H, Reynolds AP, Roach V, Safi A, Sanchez ME, Sanyal A, Shafer A, Simon JM, Song L, Vong S, Weaver M, Yan Y, Zhang Z, Lenhard B, Tewari M, Dorschner MO, Hansen RS, Navas PA, Stamatoyannopoulos G, Iyer VR, Lieb JD, Sunyaev SR, Akey JM, Sabo PJ, Kaul R, Furey TS, Dekker J, Crawford GE, Stamatoyannopoulos JA. The accessible chromatin landscape of the human genome. Nature. 2012 Sep 6;489(7414):75–82.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

75 / 82

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Mutation Rate
  • Molecular Sequence Annotation
  • Humans
  • Genomics
  • Genome, Human