title: Tissue-specific transcriptional regulation has diverged significantly between human and mouse.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
authors.forename: Robin D
authors.initials: RD
authors.lastname: Dowell
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Jacobsen
authors.forename: William
authors.initials: W
authors.lastname: Gordon
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Danford
authors.forename: Kenzie D
authors.initials: KD
authors.lastname: MacIsaac
authors.forename: P Alexander
authors.initials: PA
authors.lastname: Rolfe
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Conboy
authors.forename: David K
authors.initials: DK
authors.lastname: Gifford
authors.forename: Ernest
authors.initials: E
authors.lastname: Fraenkel
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics; D006801:Humans; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C496502:FOXA2 protein, human; C496503:Foxa2 protein, mouse; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D051559:Hepatocyte Nuclear Factor 6; C496488:Hnf1a protein, mouse; C496593:Hnf4a protein, mouse; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta