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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 publication

DOI

10.1126/science.1246426

Type

Journal article

Journal

Science

Publication Date

21/11/2014

Volume

346

Pages

1007 - 1012

Keywords

Animals, Base Sequence, Conserved Sequence, DNA, Deoxyribonuclease I, Evolution, Molecular, Genome, Human, Humans, Mice, Regulatory Sequences, Nucleic Acid, Restriction Mapping, Transcription Factors