

![]() |
Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy |
|
Authors | ![]() | |
Published in | The 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 | 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 | |
Identifiers | PMID: 17761679 | |
Full text | ||
Structures | ||
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. 32084-92. doi: 10.1074/jbc.M700899200 https://archive-ouverte.unige.ch/unige:33541 |