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Title

Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy

Authors
Keller, David M
McWeeney, Shannon
Arsenlis, Athanasios
Drouin, Jacques
Wright, Christopher V E
White, Peter
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Published in Journal of Biological Chemistry. 2007, vol. 282, no. 44, p. 32084-92
Abstract The homeobox transcription factor Pdx-1 is necessary for pancreas organogenesis and beta cell function, however, most Pdx-1-regulated genes are unknown. To further the understanding of Pdx-1 in beta cell biology, we have characterized its genomic targets in NIT-1 cells, a mouse insulinoma cell line. To identify novel targets, we developed a microarray that includes traditional promoters as well as non-coding conserved elements, micro-RNAs, and elements identified through an unbiased approach termed serial analysis of chromatin occupancy. In total, 583 new Pdx-1 target genes were identified, many of which contribute to energy sensing and insulin release in pancreatic beta cells. By analyzing 31 of the protein-coding Pdx-1 target genes, we show that 29 are expressed in beta cells and, of these, 68% are down- or up-regulated in cells expressing a dominant negative mutant of Pdx-1. We additionally show that many Pdx-1 targets also interact with NeuroD1/BETA2, including the micro-RNA miR-375, a known regulator of insulin secretion.
Keywords AnimalsBasic Helix-Loop-Helix Transcription Factors/metabolismBinding SitesCell DifferentiationChromatin/metabolismChromatin ImmunoprecipitationHomeodomain Proteins/metabolismInsulinInsulin-Secreting Cells/cytology/metabolismMiceMice, Inbred C57BLMicroRNAs/metabolismOligonucleotide Array Sequence AnalysisPolymerase Chain ReactionPromoter Regions, GeneticTrans-Activators/metabolismTranscription, Genetic
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PMID: 17761679
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KELLER, David M et al. Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy. In: Journal of Biological Chemistry, 2007, vol. 282, n° 44, p. 32084-92. https://archive-ouverte.unige.ch/unige:33541

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Deposited on : 2014-01-22

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