Journal
MOLECULAR ENDOCRINOLOGY
Volume 26, Issue 3, Pages 521-533Publisher
ENDOCRINE SOC
DOI: 10.1210/me.2011-1231
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Funding
- National Institutes of Health [P01 DK49210, U01 DK09011]
- Juvenile Diabetes Research Foundation [1-2010-72]
- Commonwealth of Pennsylvania [410043362, F30 DK085931, P30 DK19525, P30 DK50306]
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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)
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