Doris A. Stoffers The homeodomain transcription factor Pdx1 (also known as IPF1) is a master regulator of pancreas development, as mice or hu- mans 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 develop- ment and adult B-cell function, we have only rudimentary knowl- edge 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 con- servation of target genes to identify the most relevant Pdx1 tar- gets 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.
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机译：Doris A. Stoffers同源结构域转录因子Pdx1（也称为IPF1）是胰腺发育的主要调节因子，因为缺乏Pdx1功能的小鼠或人类是胰腺。重要的是，Pdx1中的杂合突变会导致人类早期和晚期糖尿病发作。尽管在发育和成年B细胞功能中起着核心作用，但我们仅了解介导这些表型的Pdx1转录组靶标的基础知识。因此，我们进行了胰岛中Pdx1占用的全球定位分析。通过对人和小鼠胰岛进行染色质免疫沉淀测序，我们使用了靶基因的进化保守性来鉴定最相关的Pdx1目标。值得注意的是，保守的靶标集中富含内分泌系统和代谢紊乱，各种信号传导途径和细胞存活的基因，为Pdx1缺乏导致的许多表型提供了分子解释。
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