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

• DOI: 10.1016/j.ydbio.2012.06.013
• Publication Date: 2012-06-26T11:43:35Z
• Authors: B.V. Gurudatta; Edward Ramos; Victor G Corces
• Keywords: Transcription, Genetic; Molecular Sequence Data; Genes, Insect; Epithelium; 03 medical and health sciences; Neoplasms; Animals; Drosophila Proteins; Eye Proteins; Molecular Biology; Cancer; Body Patterning; 0303 health sciences; Base Sequence; Cell Polarity; Cell Differentiation; Cell Biology; Chromatin; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Drosophila melanogaster; Imaginal Discs; Mutation; Epigenetics; Insulator Elements; Transcription Initiation Site; Transcription; Developmental Biology; Signal Transduction

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.