TY - JOUR
AU1 - Thurman, Robert E.
AU2 - Rynes, Eric
AU3 - Humbert, Richard
AU4 - Vierstra, Jeff
AU5 - Maurano, Matthew T.
AU6 - Haugen, Eric
AU7 - Sheffield, Nathan C.
AU8 - Stergachis, Andrew B.
AU9 - Wang, Hao
AU1 - Vernot, Benjamin
AU1 - Garg, Kavita
AU1 - John, Sam
AU1 - Sandstrom, Richard
AU1 - Bates, Daniel
AU1 - Boatman, Lisa
AU1 - Canfield, Theresa K.
AU1 - Diegel, Morgan
AU1 - Dunn, Douglas
AU1 - Ebersol, Abigail K.
AU2 - Frum, Tristan
AU2 - Giste, Erika
AU2 - Johnson, Audra K.
AU2 - Johnson, Ericka M.
AU2 - Kutyavin, Tanya
AU2 - Lajoie, Bryan
AU2 - Lee, Bum-Kyu
AU2 - Lee, Kristen
AU2 - London, Darin
AU2 - Lotakis, Dimitra
AU3 - Neph, Shane
AU3 - Neri, Fidencio
AU3 - Nguyen, Eric D.
AU3 - Qu, Hongzhu
AU3 - Reynolds, Alex P.
AU3 - Roach, Vaughn
AU3 - Safi, Alexias
AU3 - Sanchez, Minerva E.
AU3 - Sanyal, Amartya
AU3 - Shafer, Anthony
AU4 - Simon, Jeremy M.
AU4 - Song, Lingyun
AU4 - Vong, Shinny
AU4 - Weaver, Molly
AU4 - Yan, Yongqi
AU4 - Zhang, Zhancheng
AU4 - Zhang, Zhuzhu
AU4 - Lenhard, Boris
AU4 - Tewari, Muneesh
AU4 - Dorschner, Michael O.
AU5 - Hansen, R. Scott
AU5 - Navas, Patrick A.
AU5 - Stamatoyannopoulos, George
AU5 - Iyer, Vishwanath R.
AU5 - Lieb, Jason D.
AU5 - Sunyaev, Shamil R.
AU5 - Akey, Joshua M.
AU5 - Sabo, Peter J.
AU5 - Kaul, Rajinder
AU5 - Furey, Terrence S.
AU6 - Dekker, Job
AU6 - Crawford, Gregory E.
AU6 - Stamatoyannopoulos, John A.
AB - 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.
TI - The accessible chromatin landscape of the human genome
JF - Nature
DO - 10.1038/nature11232
DA - 2012-09-05
UR - https://www.deepdyve.com/lp/springer-journals/the-accessible-chromatin-landscape-of-the-human-genome-v0L04WM0Xw
SP - 75
EP - 82
VL - 489
IS - 7414
DP - DeepDyve
ER -