Functional cooperation between HP1 and DNMT1 mediates gene silencing.

Functional cooperation between HP1 and DNMT1 mediates gene silencing. Research Abstract Details 

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Functional cooperation between HP1 and DNMT1 mediates gene silencing. Abstract Text:

Andrea Smallwood,Pierre-Olivier ,Sriharsa Pradhan,Michael Carey,Andrea Smallwood,Pierre-Olivier ,Sriharsa Pradhan,Michael Carey,

Mammalian euchromatic gene silencing results from the combined repressive effects of histone and DNA methyltransferases. Little is known of the mechanism by which these enzymes cooperate to induce silencing. Here we show that mammalian HP1 family members mediate communication between histone and DNA methyltransferases. In vitro, methylation of histone 3 Lys 9 by G9a creates a binding platform for HP1alpha, beta, and gamma. DNMT1 interacts with HP1 resulting in increased DNA methylation on DNA and chromatin templates in vitro. The functional and physical interaction can be recapitulated in vivo. Binding of GAL4-HP1 to a reporter construct is sufficient to induce repression and DNA methylation in DNMT1 wild-type but not DNMT1-null cells. Additionally, silencing of the Survivin gene coincides with recruitment of G9a and HP1 in DNMT1 wild-type but not null cells. We conclude that direct interactions between HP1 and DNMT1 mediate silencing of euchromatic genes.

Functional cooperation between HP1 and DNMT1 mediates gene silencing. Publishing Authors By Initials

A Smallwood,PO ,S Pradhan,M Carey,A Smallwood,PO ,S Pradhan,M Carey,

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Functional cooperation between HP1 and DNMT1 mediates gene silencing. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Genes & development

VOLUME: 21

Page Numbers: 1169-78

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 30

MONTH: 04

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 8711660

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Grant and Affiliation Information for Functional cooperation between HP1 and DNMT1 mediates gene silencing.

AFFILIATION: Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM074701

ACRONYM: GM

MEDLINETA: Genes Dev

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