Document Detail


Foxa2-dependent hepatic gene regulatory networks depend on physiological state.
MedLine Citation:
PMID:  19417011     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bile acids are powerful detergents produced by the liver to aid in the absorption of dietary lipids. We recently reported a novel role for Foxa2 in bile acid metabolism. The winged helix transcription factor Foxa2 is required to prevent intrahepatic cholestasis and liver injury in mice fed a cholic acid-enriched diet. Here, we use functional genomics to study how Foxa2 regulates its targets in a cholic acid-dependent manner. We found that multiple signaling pathways essential for the hepatic response to acute liver injury are impaired in livers of Foxa2-deficient mice, suggesting that the deletion of Foxa2 in the hepatocyte affects the liver on a large scale. We also discovered distinct feed-forward regulatory loops controlling Foxa2-dependent targets in a cholic acid-dependent or -independent manner. We show that Foxa2 interacts with different transcription factors to achieve gene expression responses appropriate for each physiologic state.
Authors:
Irina M Bochkis; Jonathan Schug; Nir E Rubins; Atul R Chopra; Bert W O'Malley; Klaus H Kaestner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-05
Journal Detail:
Title:  Physiological genomics     Volume:  38     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-10     Completed Date:  2009-10-05     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
Affiliation:
Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cholic Acid / metabolism*
Chromatin Immunoprecipitation
Gene Expression Regulation / genetics,  physiology*
Gene Regulatory Networks / genetics,  physiology*
Genomics / methods
Hepatocyte Nuclear Factor 3-beta / genetics,  metabolism*
Liver / metabolism*
Male
Mice
Mice, Knockout
Molecular Sequence Data
Nuclear Receptor Coactivator 2 / genetics
Sequence Analysis, DNA
Signal Transduction / genetics,  physiology*
Transcription Factors / metabolism
Grant Support
ID/Acronym/Agency:
DK-049210/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Foxa2 protein, mouse; 0/Ncoa2 protein, mouse; 0/Nuclear Receptor Coactivator 2; 0/Transcription Factors; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 81-25-4/Cholic Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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