Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

作者：Vierstra Jeff; Rynes Eric; Sandstrom Richard; Zhang Miaohua; Canfield Theresa; Hansen R Scott; Stehling Sun Sandra; Sabo Peter J; Byron Rachel; Humbert Richard; Thurman Robert E; Johnson Audra K; Vong Shinny; Lee Kristen; Bates Daniel; Neri Fidencio; Diegel Morgan; Giste Erika; Haugen Eric; Dunn Douglas; Wilken Matthew S; Josefowicz Steven; Samstein Robert; Chang Kai Hsin; Eichler Evan E; De Bruijn Marella; Reh Thomas A; Skoultchi Arthur; Rudensky Alexander

来源：Science, 2014, 346(6212): 1007-1012.

DOI：10.1126/science.1246426

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.

• 出版日期2014-11-21