Characterization of Pancreatic Transcription Factor Pdx-1 Binding Sites Using Promoter Microarray and Serial Analysis of Chromatin Occupancy

Autor: Peter White, Richard H. Goodman, Claes B. Wollheim, Haiyan Wang, Athanasios Arsenlis, Klaus H. Kaestner, Shannon K. McWeeney, Christopher V.E. Wright, Jacques Drouin, David M. Keller
Rok vydání: 2007
Předmět:
Chromatin Immunoprecipitation
endocrine system
Transcription
Genetic
Biology
Polymerase Chain Reaction
Biochemistry
Chromatin/metabolism
Mice
03 medical and health sciences
0302 clinical medicine
Insulin-Secreting Cells
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
Homeodomain Proteins/metabolism
Insulin
MicroRNAs/metabolism
Trans-Activators/metabolism
ddc:612
Promoter Regions
Genetic
Molecular Biology
Gene
Transcription factor
Basic Helix-Loop-Helix Transcription Factors/metabolism
Oligonucleotide Array Sequence Analysis
030304 developmental biology
Homeodomain Proteins
0303 health sciences
Binding Sites
Cell Differentiation
Promoter
Cell Biology
Molecular biology
Chromatin
Cell biology
Mice
Inbred C57BL
MicroRNAs
medicine.anatomical_structure
030220 oncology & carcinogenesis
NEUROD1
Trans-Activators
Insulin-Secreting Cells/cytology/metabolism
Homeobox
Beta cell
Pancreas
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of Biological Chemistry, Vol. 282, No 44 (2007) pp. 32084-92
ISSN: 0021-9258
DOI: 10.1074/jbc.m700899200
Popis: 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.
Databáze: OpenAIRE
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