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Scientific article
Open access
English

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

Published inThe Journal of biological chemistry, vol. 282, no. 44, p. 32084-32092
Publication date2007
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
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Binding Sites
  • Cell Differentiation
  • Chromatin/metabolism
  • Chromatin Immunoprecipitation
  • Homeodomain Proteins/metabolism
  • Insulin
  • Insulin-Secreting Cells/cytology/metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Trans-Activators/metabolism
  • Transcription, Genetic
Citation (ISO format)
KELLER, David M et al. Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy. In: The Journal of biological chemistry, 2007, vol. 282, n° 44, p. 32084–32092. doi: 10.1074/jbc.M700899200
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Article (Published version)
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Identifiers
ISSN of the journal0021-9258
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329downloads

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