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

Jeff Vierstra, Eric Rynes, Richard Sandstrom, Miaohua Zhang, Theresa Canfield, R. Scott Hansen, Sandra Stehling-Sun, Peter J. Sabo, Rachel Byron, Richard Humbert, Robert E. Thurman, Audra K. Johnson, Shinny Vong, Kristen Lee, Daniel Bates, Fidencio Neri, Morgan Diegel, Erika Giste, Eric Haugen, Douglas DunnMatthew S. Wilken, Steven Josefowicz, Robert Samstein, Kai Hsin Chang, Evan E. Eichler, Marella De Bruijn, Thomas A. Reh, Arthur Skoultchi, Alexander Rudensky, Stuart H. Orkin, Thalia Papayannopoulou, Piper M. Treuting, Licia Selleri, Rajinder Kaul, Mark Groudine, M. A. Bender, John A. Stamatoyannopoulos

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
JournalScience
Volume346
Issue number6212
DOIs
StatePublished - Nov 21 2014

ASJC Scopus subject areas

  • General

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