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Brief Communication

Nature Genetics 39, 730–732 (1 June 2007) | doi:10.1038/ng2047

Tissue-specific transcriptional regulation has diverged significantly between human and mouse

Duncan T Odom , Robin D Dowell , Elizabeth S Jacobsen , William Gordon , Timothy W Danford , Kenzie D MacIsaac , P Alexander Rolfe , Caitlin M Conboy , David K Gifford & Ernest Fraenkel

We demonstrate that the binding sites for highly conserved transcription factors vary extensively between human and mouse. We mapped the binding of four tissue-specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, from 41% to 89% of their binding events seem to be species specific. When the same protein binds the promoters of orthologous genes, approximately two-thirds of the binding sites do not align.