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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents, Hormonal / pharmacology
-
Base Sequence
-
Blotting, Western
-
Chromatin Immunoprecipitation
-
Down-Regulation / drug effects
-
Female
-
Gene Expression Profiling
-
Gene Regulatory Networks*
-
Humans
-
Lipase / genetics
-
Lipase / metabolism
-
Male
-
Mice
-
Mice, Knockout
-
Mice, Transgenic
-
Molecular Sequence Data
-
Pancreas, Exocrine / drug effects
-
Pancreas, Exocrine / metabolism*
-
Peptide Hydrolases / genetics
-
Peptide Hydrolases / metabolism
-
Receptors, Cytoplasmic and Nuclear / genetics*
-
Receptors, Cytoplasmic and Nuclear / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sequence Homology, Amino Acid
-
Tamoxifen / pharmacology
-
Transcription Factors / genetics*
-
Transcription Factors / metabolism
Substances
-
Antineoplastic Agents, Hormonal
-
Nr5a2 protein, mouse
-
Receptors, Cytoplasmic and Nuclear
-
Transcription Factors
-
transcription factor PTF1
-
Tamoxifen
-
Lipase
-
Peptide Hydrolases