Year: 2012
Type: article
Abstract: 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 β-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.
Source: Molecular Endocrinology
DOI: 10.1210/me.2011-1231
Authors: Cynthia Khoo, Juxiang Yang, Samuel A. Weinrott, Klaus H. Kaestner, Ali Naji, Jonathan Schug, Doris A. Stoffers
Institution: University of Pennsylvania
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G311702375, G4112437853, G4218227715, G499207949, Integrative Metabolic Adaptations to Enviromental and Nutritional Challenge, G683675403, G8067760260, G8243034, G8614745718, G9000232846, University of Pennsylvania Diabetes Research Center, Center for Molecular Studies in Digestive and Liver Diseases
OpenAlex ID: W2156562915