TY - JOUR
T1 - Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy
AU - Keller, David M.
AU - McWeeney, Shannon
AU - Arsenlis, Athanasios
AU - Drouin, Jacques
AU - Wright, Christopher V.E.
AU - Wang, Haiyan
AU - Wollheim, Claes B.
AU - White, Peter
AU - Kaestner, Klaus H.
AU - Goodman, Richard H.
PY - 2007/11/2
Y1 - 2007/11/2
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M700899200
DO - 10.1074/jbc.M700899200
M3 - Article
C2 - 17761679
AN - SCOPUS:36148986076
SN - 0021-9258
VL - 282
SP - 32084
EP - 32092
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -