Tissue-specific transcriptional regulation has diverged significantly between human and mouse.
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.
Odom
Duncan T
DT
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Dowell
Robin D
RD
Jacobsen
Elizabeth S
ES
Gordon
William
W
Danford
Timothy W
TW
MacIsaac
Kenzie D
KD
Rolfe
P Alexander
PA
Conboy
Caitlin M
CM
Gifford
David K
DK
Fraenkel
Ernest
E
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
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