LRH-1 和 PTF1-L 共同调节外分泌腺特异性转录网络以实现消化功能。
LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.
机构信息
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
出版信息
Genes Dev. 2011 Aug 15;25(16):1674-9. doi: 10.1101/gad.16860911.
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.
摘要
我们已经确定了核受体肝受体同源物-1（LRH-1）在外分泌胰腺中的染色质和转录组。染色质免疫沉淀（ChIP）-seq 和 RNA-seq 分析表明，LRH-1 直接诱导编码消化酶以及分泌和线粒体蛋白的基因表达。LRH-1 与胰腺转录因子 1-L 复合物（PTF1-L）合作调节外分泌胰腺特异性基因表达。在成年小鼠中消除 LRH-1 会降低胰腺液中几种脂肪酶和蛋白酶的浓度，并损害胆囊收缩素刺激下的胰腺液分泌。因此，LRH-1 是外分泌胰腺特异性转录网络的关键调节因子，该网络对于胰腺液的产生和分泌是必需的。
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