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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in the 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 mitochrondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulationg 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. input and Lrh1 ChIP

ORGANISM(S): Mus musculus

SUBMITTER: Scott Ochsner

PROVIDER: E-GEOD-34295 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Holmstrom Sam R SR Deering Tye T Swift Galvin H GH Poelwijk Frank J FJ Mangelsdorf David J DJ Kliewer Steven A SA MacDonald Raymond J RJ

Genes & development 20110801 16

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 co ...[more]

PMID: 21852532

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

Project description:This SuperSeries is composed of the following subset Series: GSE34030: LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function [RNA-Seq] GSE34295: LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function [ChIP-Seq] Refer to individual Series

2011-12-09 | E-GEOD-34296 | biostudies-arrayexpress

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

Project description:Two separate pools of three Flox or two Lrh1t-/- pancreas RNA preparations was subjected to the Illumina RNA-seq protocol. Examination of mRNA levels in induced Lrh1 pancreas knockout and wild-type mice.

2011-11-30 | E-GEOD-34030 | biostudies-arrayexpress

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

Project description:We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in the 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 mitochrondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulationg 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.

2011-12-09 | GSE34295 | GEO

Sel1L is Indispensable for Mammalian ERAD, ER Homeostasis and Survival

Project description:Sel1L is an adaptor protein for the E3 ligase Hrd1 involved in endoplasmic reticulum-associated degradation (ERAD). Its physiological importance in mammalian ERAD, however, remains to be established. Here, using the inducible Sel1L knockout mouse and cell models, we provide the first in vivo evidence that Sel1L is indispensable for Hrd1 stability, ER homeostasis and survival. Acute loss of Sel1L leads to premature death in adult mice within 3 weeks with profound pancreatic atrophy. Contrary to current belief, our data show that mammalian Sel1L is required for Hrd1 stability and ERAD function both in vitro and in vivo. Sel1L deficiency disturbs ER homeostasis, activates ER stress, attenuates translation and promotes cell death. Serendipitously, using biochemical approach coupled with mass spectrometry, we found that Sel1L deficiency causes the aggregation of both small and large ribosomal subunits. Thus, Sel1L is an indispensable component of mammalian ERAD and ER homeostasis, which is essential for protein translation, pancreatic function, cellular and organismal survival. Pancreas tissue of wild type and inducible Sel1L knockout mice were subjected to gene expression analysis.

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Age-associated DNA methylation increases in mouse pancreatic islets suggest an epigenetic drift toward the exocrine pancreas epigenome

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2014-12-03 | E-GEOD-63811 | biostudies-arrayexpress

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Comparative gene expression of mouse Pancreatic specific transcription factor 1a (Ptf1a/p48) in pancreatic progenitor cells

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2011-01-24 | E-GEOD-26816 | biostudies-arrayexpress

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Project description:Several miRNAs have tissue-specific patterns consistent with crucial functions in many biological processes and are candidate biomarkers of disease. Yet, there is limited knowledge about the role of pancreas-specific miRNAs in pancreatic pathologies. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. By profiling miRNAs from human islets and subsequent systematic tissue analysis we found that miR-216a is highly enriched in endocrine and exocrine pancreas. Deletion of miR-216a in mice lead to a reduction in islet size, β-cell mass and insulin levels. RNA-sequencing indicated that cell cycle and proliferation were the most significantly regulated biological processes in miR-216 knockout pancreata. miR-216a was induced by TGF-β signalling and inhibition of miR-216a increased apoptosis and decreased cell proliferation in both β- and exocrine cells. Deletion of miR-216a in the pancreatic cancer prone mouse line Kras G12D ;Ptf1a CreER reduced the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels were elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA but also suggests miR-216a as a promising biomarker for diagnosis of pancreatic diseases.

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