title: 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.
authors.affiliation: New England Biolabs Incorporated, 240 County Road, Ipswich, MA 01938, USA.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Estève
authors.forename: Hang Gyeong
authors.initials: HG
authors.lastname: Chin
authors.forename: Jack
authors.initials: J
authors.lastname: Benner
authors.forename: George R
authors.initials: GR
authors.lastname: Feehery
authors.forename: Mala
authors.initials: M
authors.lastname: Samaranayake
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Horwitz
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Sriharsa
authors.initials: S
authors.lastname: Pradhan
mesh_terms: 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
chemical_list: 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