Research resource: the pdx1 cistrome of pancreatic islets

Mol Endocrinol. 2012 Mar;26(3):521-33. doi: 10.1210/me.2011-1231. Epub 2012 Feb 9.

Abstract

The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mutations in Pdx1 cause early and late onset forms of diabetes in humans. Despite these central roles in development and adult β-cell function, we have only rudimentary knowledge of the transcriptome targets of Pdx1 that mediate these phenotypes. Therefore, we performed global location analysis of Pdx1 occupancy in pancreatic islets. We used evolutionary conservation of target genes to identify the most relevant Pdx1 targets by performing chromatin immunoprecipitation sequencing on both human and mouse islets. Remarkably, the conserved target set is highly enriched for genes annotated to function in endocrine system and metabolic disorders, various signaling pathways, and cell survival, providing a molecular explanation for many of the phenotypes resulting from Pdx1 deficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Chromatin Immunoprecipitation
  • Consensus Sequence
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology*
  • Humans
  • Islets of Langerhans / metabolism*
  • Mice
  • Protein Binding
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sequence Analysis, DNA
  • Trans-Activators / deficiency
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcriptional Activation*

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Homeodomain Proteins
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein