VEZF1 elements mediate protection from DNA methylation

Dickson, J., Gowher, H., Strogantsev, R., Gaszner, M., Hair, A., Felsenfeld, G. and West, A. G. (2010) VEZF1 elements mediate protection from DNA methylation. PLoS Genetics, 6(1), e1000804. (doi: 10.1371/journal.pgen.1000804)

Abstract

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: West, Dr Adam and Strogantsev, Mr Ruslan and Hair, Dr Alan and Dickson, Dr Jacqueline
• Authors: Dickson, J., Gowher, H., Strogantsev, R., Gaszner, M., Hair, A., Felsenfeld, G., and West, A. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7404
• Copyright Holders: Copyright © 2010 The Authors
• First Published: First published in PLoS Genetics 6(1):e1000804
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

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Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
38191	1	Understanding chromatin insulator elements and their roles in gene transcription	Adam West	Medical Research Council (MRC)	G0400180	Institute of Cancer Sciences