Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.
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.
Estève
Pierre-Olivier
PO
New England Biolabs Incorporated, 240 County Road, Ipswich, MA 01938, USA.
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
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002522:Chlorocebus aethiops; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D004795:Enzyme Stability; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection
D034741:RNA, Small Interfering; D000076983:Histone Methyltransferases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine