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.
Bibliographical noteFunding Information:
This work was supported by funding from US National Institutes of Health (grants DK68655 and DK70813 (D.T.O.) and DK076284 (R.D.D.)), Cancer Research UK (D.T.O.) and the Whitaker Foundation (E.F.).