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)

[img]
Preview
Text
36517.pdf

1MB

Publisher's URL: http://dx.doi.org/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 > Institute 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
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381911Understanding chromatin insulator elements and their roles in gene transcriptionAdam WestMedical Research Council (MRC)G0400180Institute of Cancer Sciences