Research Resource: The Pdx1 Cistrome of Pancreatic Islets
Research Resource: The Pdx1 Cistrome of Pancreatic Islets
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DOI：
10.1210/me.2011-1231
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发表时间：
2012-03-01
影响因子：
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通讯作者：
Stoffers, Doris A.
中科院分区：
文献类型：
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作者：
Khoo, Cynthia;Yang, Juxiang;Stoffers, Doris A.
同源域转录因子胰腺十二指肠同源框1（Pdx 1，也称为胰岛素启动子因子1）是胰腺发育的主要调节因子，因为缺乏Pdx 1功能的小鼠或人类是胰腺。重要的是，Pdx 1的杂合突变导致人类早期和晚期糖尿病。尽管在发育和成人β细胞功能中发挥着这些核心作用，但我们对介导这些表型的Pdx 1转录组靶点只有初步了解。因此，我们对胰岛中的Pdx 1占用进行了全局定位分析。我们利用靶基因的进化保守性，通过对人和小鼠胰岛进行染色质免疫沉淀测序来鉴定最相关的Pdx 1靶点。值得注意的是，保守的目标集是高度富集的基因注释功能的内分泌系统和代谢紊乱，各种信号传导途径，和细胞存活，提供了一个分子解释的许多表型所造成的Pdx 1缺陷。（分子内分泌学26：521-533，2012）
The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mutations in Pdx1 cause early and late onset forms of diabetes in humans. Despite these central roles in development and adult beta-cell function, we have only rudimentary knowledge of the transcriptome targets of Pdx1 that mediate these phenotypes. Therefore, we performed global location analysis of Pdx1 occupancy in pancreatic islets. We used evolutionary conservation of target genes to identify the most relevant Pdx1 targets by performing chromatin immunoprecipitation sequencing on both human and mouse islets. Remarkably, the conserved target set is highly enriched for genes annotated to function in endocrine system and metabolic disorders, various signaling pathways, and cell survival, providing a molecular explanation for many of the phenotypes resulting from Pdx1 deficiency. (Molecular Endocrinology 26: 521-533, 2012)