期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 13, 页码 5076-5081出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0810362106
关键词
DNA methyltransferase; methylated lysine; proteasome; protein degradation
资金
- National Institutes of Health [GM60398]
- Investigator of the Howard Hughes Medical Institute
- National Cancer Institute Award [F32CA137995]
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. 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.
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