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 journalArticle

59 Citations (Scopus)

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

Fingerprint

Exocrine Pancreas
Gene Regulatory Networks
Pancreas
Transcription Factors
Liver
Fluids and Secretions
Gene Expression
Chromatin Immunoprecipitation
Mitochondrial Proteins
Cholecystokinin
Cytoplasmic and Nuclear Receptors
Lipase
Transcriptome
Peptide Hydrolases
RNA
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function. / Holmstrom, Sam R.; Deering, Tye; Swift, Galvin H.; Poelwijk, Frank J.; Mangelsdorf, David J.; Kliewer, Steven A.; Macdonald, Raymond J.

In: Genes and Development, Vol. 25, No. 16, 15.08.2011, p. 1674-1679.

Research output: Contribution to journalArticle

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