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Originally published In Press as doi:10.1074/jbc.M103921200 on August 27, 2001

J. Biol. Chem., Vol. 276, Issue 44, 40778-40787, November 2, 2001
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Demethylase Activity Is Directed by Histone Acetylation*

Nadia Cervoni and Moshe SzyfDagger

From the Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ H3G 1Y6, Canada

Mammalian genomes are compartmentalized into dense inactive chromatin that is hypermethylated and active open chromatin that is hypomethylated. It is generally accepted that this bimodal pattern of methylation is established during development and is then faithfully inherited through subsequent cell divisions by a maintenance DNA methyltransferase (DNMT1). The pattern of methylation is believed to direct local histone acetylation states. In contrast to this well accepted consensus, we show here using a transient transfection model that an active demethylase is involved in shaping patterns of methylation in somatic cells. Demethylase activity is directed by the state of histone acetylation, and therefore, the resulting methylation pattern is determined by local histone acetylation states contrary to the accepted model. Our data support a new model suggesting that the pattern of methylation is maintained by a dynamic balance of methylation and demethylation activities and the local state of histone acetylation. This provides a simple mechanism for explaining why active genes are not methylated.

* This work was supported by a grant from the Canadian Institute of Health Research (to M. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pharmacology and Therapeutics, McGill University, 3655 Drummond St., Montreal PQ H3G 1Y6, Canada. Tel.: 514-398-7107; Fax: 514-398-6690; E-mail: mszyf@pharma.mcgill.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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