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...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2009-03, Vol.106 (13), p.5076-5081
Hauptverfasser: Estève, Pierre-Olivier, Chin, Hang Gyeong, Benner, Jack, Feehery, George R., Samaranayake, Mala, Horwitz, Gregory A., Jacobsen, Steven E., Pradhan, Sriharsa, Rine, Jasper
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container_issue 13
container_start_page 5076
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 106
creator Estève, Pierre-Olivier
Chin, Hang Gyeong
Benner, Jack
Feehery, George R.
Samaranayake, Mala
Horwitz, Gregory A.
Jacobsen, Steven E.
Pradhan, Sriharsa
Rine, Jasper
description 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 DNMTL SET7 co loca lizes and directly interacts with DNMT1 and specifically monomethylates Lys-142 of DNMTL 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 DNMTL These results demonstrate that signaling through SET7 represents a means of DNMT1 enzyme turnover.
doi_str_mv 10.1073/pnas.0810362106
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subjects Amino acids
Animals
Antibodies
Biological Sciences
Cell Cycle
Cercopithecus aethiops
COS Cells
DNA
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - metabolism
Enzyme Stability
Gene expression regulation
HeLa Cells
Histone-Lysine N-Methyltransferase - genetics
Histone-Lysine N-Methyltransferase - physiology
Histones
Humans
Lysine - metabolism
Methylation
RNA, Small Interfering - pharmacology
T lymphocytes
Transfection
title Regulation of DNMT1 Stability through Set7-Mediated Lysine Methylation in Mammalian Cells
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