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

448 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

N1 - 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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N2 - 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.

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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EP - 732

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

Abstract

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