Drosophila CTCF tandemly aligns with other insulator proteins at the borders of H3K27me3 domains

• Type of Material: Article
• Authors: Kevin Van Bortle, Emory University; Edward Ramos, Emory University; Naomi Takenaka, Emory University; Jingping Yang, Emory University; Jessica E. Wahi, Emory University; Victor Corces, Emory University
• Language: English
• Date: 2012-11
• Publisher: Cold Spring Harbor Laboratory Press
• Publication Version: Final Published Version
• Copyright Statement: 2012, Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License)
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://genome.cshlp.org/content/22/11/2176
• Title of Journal or Parent Work: Genome Research
• ISSN: 1088-9051
• Volume: 22
• Issue: 11
• Start Page: 2176
• End Page: 2187
• Grant/Funding Information: This work was supported by U.S. Public Health Service Awards to V.G.C. (GM35463) and E.R. (CA133106) from the National Institutes of Health.
• Research Categories: Biology, General

Abstract

Several multiprotein DNA complexes capable of insulator activity have been identified in Drosophila melanogaster, yet only CTCF, a highly conserved zinc finger protein, and the transcription factor TFIIIC have been shown to function in mammals. CTCF is involved in diverse nuclear activities, and recent studies suggest that the proteins with which it associates and the DNA sequences that it targets may underlie these various roles. Here we show that the Drosophila homolog of CTCF (dCTCF) aligns in the genome with other Drosophila insulator proteins such as Suppressor of Hairy wing [SU(HW)] and Boundary Element Associated Factor of 32 kDa (BEAF-32) at the borders of H3K27me3 domains, which are also enriched for associated insulator proteins and additional cofactors. RNAi depletion of dCTCF and combinatorial knockdown of gene expression for other Drosophila insulator proteins leads to a reduction in H3K27me3 levels within repressed domains, suggesting that insulators are important for the maintenance of appropriate repressive chromatin structure in Polycomb (Pc) domains. These results shed new insights into the roles of insulators in chromatin domain organization and support recent models suggesting that insulators underlie interactions important for Pc-mediated repression. We reveal an important relationship between dCTCF and other Drosophila insulator proteins and speculate that vertebrate CTCF may also align with other nuclear proteins to accomplish similar functions.