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Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.

ABSTRACT: Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltransferase (DNMT1). Here, we show that SET7, a known histone methyltransferase, is involved in the regulation of protein stability of DNMT1. SET7 colocalizes and directly interacts with DNMT1 and specifically monomethylates Lys-142 of DNMT1. Methylated DNMT1 peaks during the S and G(2) phases of the cell cycle and is prone to proteasome-mediated degradation. Overexpression of SET7 leads to decreased DNMT1 levels, and siRNA-mediated knockdown of SET7 stabilizes DNMT1. These results demonstrate that signaling through SET7 represents a means of DNMT1 enzyme turnover.

SUBMITTER: Esteve PO

PROVIDER: S-EPMC2654809 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.

Estève Pierre-Olivier PO Chin Hang Gyeong HG Benner Jack J Feehery George R GR Samaranayake Mala M Horwitz Gregory A GA Jacobsen Steven E SE Pradhan Sriharsa S

Proceedings of the National Academy of Sciences of the United States of America 20090312 13

Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltransferase (DNMT1). Here, we show that SET7, a known histone methyltransferase, is involved in the regulation of protein stability of DNMT1. SET7 colocalizes and directly interacts with DNMT1 and specifically monomethylates Lys-142 of DNMT1. Methylated DNMT1 peaks during the S and G(2) phases of the cell cycle ...[more]

PMID: 19282482

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Project description:This SuperSeries is composed of the SubSeries listed below.

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