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

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

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)32084-32092
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number44
DOIs
StatePublished - Nov 2 2007

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Microarray Analysis
Microarrays
Chromatin
Transcription Factors
Genes
Binding Sites
MicroRNAs
Cells
Cytology
Insulin
Insulinoma
Organogenesis
Homeobox Genes
Insulin-Secreting Cells
Cell Biology
Pancreas
Cell Line
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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 B.; White, Peter; Kaestner, Klaus H.; Goodman, Richard.

In: Journal of Biological Chemistry, Vol. 282, No. 44, 02.11.2007, p. 32084-32092.

Research output: Contribution to journalArticle

Keller, David M. ; McWeeney, Shannon ; Arsenlis, Athanasios ; Drouin, Jacques ; Wright, Christopher V E ; Wang, Haiyan ; Wollheim, Claes B. ; White, Peter ; Kaestner, Klaus H. ; Goodman, Richard. / 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, No. 44. pp. 32084-32092.
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