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

Sam R. Holmstrom, Tye Deering, Galvin H. Swift, Frank J. Poelwijk, David J. Mangelsdorf, Steven A. Kliewer, Raymond J. Macdonald

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

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 transcrip-tional network required for the production and secretion of pancreatic fluid.

Original languageEnglish (US)
Pages (from-to)1674-1679
Number of pages6
JournalGenes and Development
Volume25
Issue number16
DOIs
StatePublished - Aug 15 2011

Keywords

  • ChIP-seq
  • Digestive enzymes
  • Exocrine pancreas
  • LRH-1
  • PTF1-L
  • RNA-seq

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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