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 |
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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. |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0810362106</identifier><identifier>PMID: 19282482</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2009-03, Vol.106 (13), p.5076-5081</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-4e261becb59d8b7711fc87ac5cf833f0b4465766f269fb44992f4862d30967663</citedby><cites>FETCH-LOGICAL-c567t-4e261becb59d8b7711fc87ac5cf833f0b4465766f269fb44992f4862d30967663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/106/13.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40455151$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40455151$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27926,27927,53793,53795,58019,58252</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19282482$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Estève, Pierre-Olivier</creatorcontrib><creatorcontrib>Chin, Hang Gyeong</creatorcontrib><creatorcontrib>Benner, Jack</creatorcontrib><creatorcontrib>Feehery, George R.</creatorcontrib><creatorcontrib>Samaranayake, Mala</creatorcontrib><creatorcontrib>Horwitz, Gregory A.</creatorcontrib><creatorcontrib>Jacobsen, Steven E.</creatorcontrib><creatorcontrib>Pradhan, Sriharsa</creatorcontrib><creatorcontrib>Rine, Jasper</creatorcontrib><title>Regulation of DNMT1 Stability through Set7-Mediated Lysine Methylation in Mammalian Cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><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.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>Cell Cycle</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>Enzyme Stability</subject><subject>Gene expression regulation</subject><subject>HeLa Cells</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Histone-Lysine N-Methyltransferase - physiology</subject><subject>Histones</subject><subject>Humans</subject><subject>Lysine - metabolism</subject><subject>Methylation</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>T lymphocytes</subject><subject>Transfection</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuP0zAURi0EYjoDa1ZAVohNZq7f9gYJlafUgsQMC1aWk9itR05SYgdN_z2pGk1hAyvL9vmO7tWH0DMMlxgkvdp1Nl2CwkAFwSAeoAUGjUvBNDxECwAiS8UIO0PnKd0CgOYKHqMzrIkiTJEF-vHNbcZoc-i7ovfFuy_rG1xcZ1uFGPK-yNuhHzfb4tplWa5dE2x2TbHap9C5Yu3ydj9nQ1esbdvaGGxXLF2M6Ql65G1M7ul8XqDvH97fLD-Vq68fPy_frsqaC5lL5ojAlasrrhtVSYmxr5W0Na-9otRDxZjgUghPhPbTRWvimRKkoaDF9E4v0JujdzdWrWtq1-XBRrMbQmuHveltMH__dGFrNv0vQwRnCvQkeDULhv7n6FI2bUj1tILtXD8mIyRoTbX8L0iAUEo0nsCrI1gPfUqD8_fTYDCH3syhN3PqbUq8-HOJEz8XNQEvZ-CQPOmEwdRwkAfF638Txo8xZneXJ_T5Eb1NuR_uWQaMc8wx_Q1_pbWr</recordid><startdate>20090331</startdate><enddate>20090331</enddate><creator>Estève, Pierre-Olivier</creator><creator>Chin, Hang Gyeong</creator><creator>Benner, Jack</creator><creator>Feehery, George R.</creator><creator>Samaranayake, Mala</creator><creator>Horwitz, Gregory A.</creator><creator>Jacobsen, Steven E.</creator><creator>Pradhan, Sriharsa</creator><creator>Rine, Jasper</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090331</creationdate><title>Regulation of DNMT1 Stability through Set7-Mediated Lysine Methylation in Mammalian Cells</title><author>Estève, Pierre-Olivier ; 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>19282482</pmid><doi>10.1073/pnas.0810362106</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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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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