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The negative effects of bile acids and tumor necrosis factor-alpha on the transcription of cholesterol 7alpha-hydroxylase gene (CYP7A1) converge to hepatic nuclear factor-4: a novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors

De Fabiani, E.; Mitro, N.; Anzulovich, A.C.; Pinelli, A.; Galli, G.; Crestani, M.

Journal of Biological Chemistry 276(33): 30708-30716

2001


ISSN/ISBN: 0021-9258
PMID: 11402042
DOI: 10.1074/jbc.m103270200
Accession: 011528003

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Bile acids regulate the cholesterol 7alpha-hydroxylase gene (CYP7A1), which encodes the rate-limiting enzyme in the classical pathway of bile acid synthesis. Here we report a novel mechanism whereby bile acid feedback regulates CYP7A1 transcription through the nuclear receptor hepatocyte nuclear factor-4 (HNF-4), which binds to the bile acid response element (BARE) at nt -149/-118 relative to the transcription start site.

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