The BEAF insulator regulates genes involved in cell polarity and neoplastic growth

Dev Biol. 2012 Sep 1;369(1):124-32. doi: 10.1016/j.ydbio.2012.06.013. Epub 2012 Jun 26.

Abstract

Boundary Element Associated Factor-32 (BEAF-32) is an insulator protein predominantly found near gene promoters and thought to play a role in gene expression. We find that mutations in BEAF-32 are lethal, show loss of epithelial morphology in imaginal discs and cause neoplastic growth defects. To investigate the molecular mechanisms underlying this phenotype, we carried out a genome-wide analysis of BEAF-32 localization in wing imaginal disc cells. Mutation of BEAF-32 results in miss-regulation of 3850 genes by at least 1.5-fold, 794 of which are bound by this protein in wing imaginal cells. Up-regulated genes encode proteins involved in cell polarity, cell proliferation and cell differentiation. Among the down-regulated genes are those encoding components of the wingless pathway, which is required for cell differentiation. Miss-regulation of these genes explains the unregulated cell growth and neoplastic phenotypes observed in imaginal tissues of BEAF-32 mutants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Polarity / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Epithelium / metabolism
  • Epithelium / pathology
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Insect / genetics*
  • Imaginal Discs / metabolism
  • Insulator Elements / genetics*
  • Molecular Sequence Data
  • Mutation / genetics
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Signal Transduction / genetics
  • Transcription Initiation Site
  • Transcription, Genetic
  • Up-Regulation / genetics
  • Wings, Animal / metabolism

Substances

  • BEAF-32 protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins