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Journal Articles Journal of Biological Chemistry Year : 2003

Liver Receptor Homolog 1 Controls the Expression of Carboxyl Ester Lipase

Abstract

The orphan nuclear receptor liver receptor homolog 1 (LRH-1) plays a central role in cholesterol homeostasis by regulating a number of hepatic and intestinal genes critical for reverse cholesterol transport and bile acid homeostasis. Herein, we describe the identification of carboxyl ester lipase (CEL) as a novel target of LRH-1 in pancreas, a tissue in which LRH-1 is abundantly expressed. In situ hybridization and gene expression studies demonstrate that both LRH-1 and CEL are co-expressed and confined to the exocrine pancreas. LRH-1 interacts with a consensus LRH-1 response element in the human CEL promoter, which is perfectly conserved in the rat gene, and induces CEL promoter activity in cotransfection assays. As reported for other LRH-1 target genes, the nuclear receptor short heterodimer partner represses LRH-1-induced CEL promoter activity. Chromatin immunoprecipitation demonstrates that binding of LRH-1 to the CEL promoter increases histone H4 acetylation corresponding with the activation of endogenous CEL gene transcription. Our data, identifying CEL as the first pancreatic LRH-1 target gene, indicate that LRH-1 is an important player in enterohepatic cholesterol homeostasis.
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Origin : Publication funded by an institution

Dates and versions

hal-04145721 , version 1 (29-06-2023)

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Elisabeth Fayard, Kristina Schoonjans, Jean-Sébastien Annicotte, Johan Auwerx. Liver Receptor Homolog 1 Controls the Expression of Carboxyl Ester Lipase. Journal of Biological Chemistry, 2003, 278 (37), pp.35725 - 35731. ⟨10.1074/jbc.m302370200⟩. ⟨hal-04145721⟩
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