LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.

Holmstrom SR, Deering T, Swift GH, Poelwijk FJ, Mangelsdorf DJ, Kliewer SA, MacDonald RJ
Genes Dev. 2011 25 (16): 1674-9

PMID: 21852532 · PMCID: PMC3165932 · DOI:10.1101/gad.16860911

We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulating exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid.

MeSH Terms (23)

Animals Antineoplastic Agents, Hormonal Base Sequence Blotting, Western Chromatin Immunoprecipitation Down-Regulation Female Gene Expression Profiling Gene Regulatory Networks Humans Lipase Male Mice Mice, Knockout Mice, Transgenic Molecular Sequence Data Pancreas, Exocrine Peptide Hydrolases Receptors, Cytoplasmic and Nuclear Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Tamoxifen Transcription Factors

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