title: LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.
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 transcriptional network required for the production and secretion of pancreatic fluid.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Sam R
authors.initials: SR
authors.lastname: Holmstrom
authors.forename: Tye
authors.initials: T
authors.lastname: Deering
authors.forename: Galvin H
authors.initials: GH
authors.lastname: Swift
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Poelwijk
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C062602:transcription factor PTF1; D013629:Tamoxifen; D008049:Lipase; D010447:Peptide Hydrolases