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

Keller, David M; McWeeney, Shannon; Arsenlis, Athanasios; Drouin, Jacques; Wright, Christopher V E; Wang, Haiyan; Wollheim, Claes; White, Peter; Kaestner, Klaus H; Goodman, Richard H

doi:10.1074/jbc.M700899200

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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 Wang, Haiyan Wollheim, Claes White, Peter Kaestner, Klaus H Goodman, Richard H show all authors [1 - 10]
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		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		DOI: 10.1074/jbc.M700899200 PMID: 17761679
Full text		Article (Published version) (437 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
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: Journal of Biological Chemistry, 2007, vol. 282, n° 44, p. 32084-92. doi: 10.1074/jbc.M700899200 https://archive-ouverte.unige.ch/unige:33541