Publikationsdatum:
2012-09-08
Beschreibung:
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 approximately 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 approximately 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721348/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thurman, Robert E -- Rynes, Eric -- Humbert, Richard -- Vierstra, Jeff -- Maurano, Matthew T -- Haugen, Eric -- Sheffield, Nathan C -- Stergachis, Andrew B -- Wang, Hao -- Vernot, Benjamin -- Garg, Kavita -- John, Sam -- Sandstrom, Richard -- Bates, Daniel -- Boatman, Lisa -- Canfield, Theresa K -- Diegel, Morgan -- Dunn, Douglas -- Ebersol, Abigail K -- Frum, Tristan -- Giste, Erika -- Johnson, Audra K -- Johnson, Ericka M -- Kutyavin, Tanya -- Lajoie, Bryan -- Lee, Bum-Kyu -- Lee, Kristen -- London, Darin -- Lotakis, Dimitra -- Neph, Shane -- Neri, Fidencio -- Nguyen, Eric D -- Qu, Hongzhu -- Reynolds, Alex P -- Roach, Vaughn -- Safi, Alexias -- Sanchez, Minerva E -- Sanyal, Amartya -- Shafer, Anthony -- Simon, Jeremy M -- Song, Lingyun -- Vong, Shinny -- Weaver, Molly -- Yan, Yongqi -- Zhang, Zhancheng -- Zhang, Zhuzhu -- Lenhard, Boris -- Tewari, Muneesh -- Dorschner, Michael O -- Hansen, R Scott -- Navas, Patrick A -- Stamatoyannopoulos, George -- Iyer, Vishwanath R -- Lieb, Jason D -- Sunyaev, Shamil R -- Akey, Joshua M -- Sabo, Peter J -- Kaul, Rajinder -- Furey, Terrence S -- Dekker, Job -- Crawford, Gregory E -- Stamatoyannopoulos, John A -- F30 DK095678/DK/NIDDK NIH HHS/ -- GM076036/GM/NIGMS NIH HHS/ -- HG004563/HG/NHGRI NIH HHS/ -- HG004592/HG/NHGRI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- MC_UP_1102/1/Medical Research Council/United Kingdom -- P30 CA016086/CA/NCI NIH HHS/ -- R01 GM076036/GM/NIGMS NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- R01 MH084676/MH/NIMH NIH HHS/ -- R01MH084676/MH/NIMH NIH HHS/ -- U54 HG004563/HG/NHGRI NIH HHS/ -- U54 HG004592/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):75-82. doi: 10.1038/nature11232.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955617" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Chromatin/*genetics/*metabolism
;
DNA/*genetics
;
DNA Footprinting
;
DNA Methylation
;
DNA-Binding Proteins/metabolism
;
Deoxyribonuclease I/metabolism
;
*Encyclopedias as Topic
;
Evolution, Molecular
;
Genome, Human/*genetics
;
Genomics
;
Humans
;
*Molecular Sequence Annotation
;
Mutation Rate
;
Promoter Regions, Genetic/genetics
;
Regulatory Sequences, Nucleic Acid/*genetics
;
Transcription Factors/metabolism
;
Transcription Initiation Site
;
Transcription, Genetic
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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