The accessible chromatin landscape of the human genome
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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
Sandstrom, Richard
Bates, Daniel
Canfield, Theresa K.
Diegel, Morgan
Dunn, Douglas
Ebersol, Abigail K.
Frum, Tristan
Giste, Erika
Harding, Lisa
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.
Reynolds, Alex P.
Roach, Vaughn
Safi, Alexias
Sanchez, Minerva E.
Sanyal, Amartya
Shafer, Anthony
Simon, Jeremy M.
Song, Lingyun
Vong, Shinny
Weaver, Molly
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.
Akey, Joshua M.
Sabo, Peter J.
Kaul, Rajinder
Furey, Terrence S.
Dekker, Job
Crawford, Gregory E.
Stamatoyannopoulos, John A.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nature11232Metadata
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Thurman, R. E., E. Rynes, R. Humbert, J. Vierstra, M. T. Maurano, E. Haugen, N. C. Sheffield, et al. 2013. “The accessible chromatin landscape of the human genome.” Nature 489 (7414): 75-82. doi:10.1038/nature11232. http://dx.doi.org/10.1038/nature11232.Abstract
DNaseI 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 choreographed with dozens to hundreds of co-activated elements, and the trans-cellular DNaseI sensitivity pattern at a given region can predict cell type-specific functional behaviors. 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721348/pdf/Terms of Use
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