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Foxa2-dependent hepatic gene regulatory networks depend on physiological state.

ABSTRACT: 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.

SUBMITTER: Bochkis IM

PROVIDER: S-EPMC2712224 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Foxa2-dependent hepatic gene regulatory networks depend on physiological state.

Bochkis Irina M IM Schug Jonathan J Rubins Nir E NE Chopra Atul R AR O'Malley Bert W BW Kaestner Klaus H KH

Physiological genomics 20090505 2

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 res ...[more]

PMID: 19417011

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