| Literature DB >> 25411453 |
Jeff Vierstra1, Eric Rynes1, Richard Sandstrom1, Miaohua Zhang2, Theresa Canfield1, R Scott Hansen3, Sandra Stehling-Sun1, Peter J Sabo1, Rachel Byron2, Richard Humbert1, Robert E Thurman1, Audra K Johnson1, Shinny Vong1, Kristen Lee1, Daniel Bates1, Fidencio Neri1, Morgan Diegel1, Erika Giste1, Eric Haugen1, Douglas Dunn1, Matthew S Wilken4, Steven Josefowicz5, Robert Samstein5, Kai-Hsin Chang6, Evan E Eichler7, Marella De Bruijn8, Thomas A Reh4, Arthur Skoultchi9, Alexander Rudensky5, Stuart H Orkin10, Thalia Papayannopoulou6, Piper M Treuting11, Licia Selleri12, Rajinder Kaul13, Mark Groudine14, M A Bender15, John A Stamatoyannopoulos16.
Abstract
To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.Entities:
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Year: 2014 PMID： 25411453 PMCID： PMC4337786 DOI： 10.1126/science.1246426
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728