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PMID: 17529977 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 39 ·No. 6 ·2007-06-00 ·Pages 730-2

Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, Rolfe PA, Conboy CM, Gifford DK, Fraenkel E

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.

MeSH Terms
Animals Conserved Sequence/genetics Gene Expression Regulation Genetic Variation Hepatocyte Nuclear Factor 1-alpha/genetics Hepatocyte Nuclear Factor 3-beta/genetics Hepatocyte Nuclear Factor 4/genetics Hepatocyte Nuclear Factor 6/genetics Humans Mice Regulatory Sequences, Nucleic Acid Sequence Homology Transcription Factors/genetics Transcription, Genetic
Chemicals
FOXA2 protein, human Foxa2 protein, mouse HNF1A protein, human HNF4A protein, human Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 4 Hepatocyte Nuclear Factor 6 Hnf1a protein, mouse Hnf4a protein, mouse Transcription Factors Hepatocyte Nuclear Factor 3-beta
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Odom Duncan T
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Dowell Robin D
Jacobsen Elizabeth S
Gordon William
Danford Timothy W
MacIsaac Kenzie D
Rolfe P Alexander
Conboy Caitlin M
Gifford David K
Fraenkel Ernest
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1061-4036
DOI
10.1038/ng2047
Published
2007-06-00
Epub
2007-00-21
Pages
730-2
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3797512
Subset
IM
Grants
NIDDK NIH HHS · DK70813 · United States
NIDDK NIH HHS · K25 DK070813 · United States
NIDDK NIH HHS · F32 DK076284 · United States
NIDDK NIH HHS · DK68655 · United States
NIDDK NIH HHS · R01 DK068655 · United States
NIDDK NIH HHS · DK92310 · United States
Cancer Research UK · 15603 · United Kingdom
NIDDK NIH HHS · DK076284 · United States
NLM NIH HHS · N01DK92310 · United States
Cancer Research UK · A15603 · United Kingdom
External Links
PubMed source DOI: 10.1038/ng2047 PMC Full Text View journal details
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