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

• Type of Material: Article
• Authors: B.V. Gurudatta, Emory University; Edward Ramos, Emory University; Victor Corces, Emory University
• Language: English
• Date: 2012-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ydbio.2012.06.013
• Title of Journal or Parent Work: Developmental Biology
• ISSN: 0012-1606
• Volume: 369
• Issue: 1
• Start Page: 124
• End Page: 132
• Grant/Funding Information: This work was supported by U.S. Public Health Service Award GM35463 from the National Institutes of Health.
• Keywords: Cancer; Epigenetics; Transcription; Chromatin
• Research Categories: Biology, Genetics; Biology, General; Health Sciences, Oncology

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.