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

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

Medical School - Twin Cities Campus

Research output: Contribution to journal › Article › peer-review

437 Scopus citations

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.

Original language	English (US)
Pages (from-to)	730-732
Number of pages	3
Journal	Nature Genetics
Volume	39
Issue number	6
DOIs	https://doi.org/10.1038/ng2047
State	Published - Jun 2007

Bibliographical note

Funding 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.).

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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.",

author = "Odom, {Duncan T.} and Dowell, {Robin D.} and Jacobsen, {Elizabeth S.} and William Gordon and Danford, {Timothy W.} and MacIsaac, {Kenzie D.} and Rolfe, {P. Alexander} and Conboy, {Caitlin M.} and Gifford, {David K.} and Ernest Fraenkel",

note = "Funding 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.).",

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AU - Odom, Duncan T.

AU - Dowell, Robin D.

AU - Jacobsen, Elizabeth S.

AU - Gordon, William

AU - Danford, Timothy W.

AU - MacIsaac, Kenzie D.

AU - Rolfe, P. Alexander

AU - Conboy, Caitlin M.

AU - Gifford, David K.

AU - Fraenkel, Ernest

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AB - 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.

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

Abstract

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