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TET2 promotes histone O-GlcNAcylation during gene transcription

机译：TET2在基因转录过程中促进组蛋白O-GlcNAcylation

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摘要

TET家族的酶催化5-甲基胞嘧啶(DNA中的第rn5个碱基)被氧化为衍生物如5-羟甲基胞嘧啶rn的反应，还能影响基因表达。在这项研究中，rnXiaochun Yu及其同事发现，TET2与O-linked-rnN-acetylglucosamine transferase(OGT)结合，rn后者是一种催化O-GicNAcylation反应的酶：而rn且这两种蛋白同时在转录起始点上被发现。rnTET2促进OGT在组蛋白H2B的O-GlcNAcylationrn反应(与活性基因相关的一个组蛋白标记)中rn的活性。因此，除了影响组蛋白修饰外，rnTET2还影响在转录调控中有潜在重要性的rnDNA修饰。%Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine and regulate gene transcription. However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive. Using protein affinity purification, here we search for functional partners of TET proteins, and find that TET2 and TET3 associate with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation) in vivo TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription start sites. Down-regulation of TET2 reduces the amount of histone 2B Serll2 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription.
机译：TET家族的酶催化5-甲基胞嘧啶(DNA中的第rn5个碱基)被氧化为衍生物如5-羟甲基胞嘧啶rn的反应，还能影响基因表达。在这项研究中，rnXiaochun Yu及其同事发现，TET2与O-linked-rnN-acetylglucosamine transferase(OGT)结合，rn后者是一种催化O-GicNAcylation反应的酶：而rn且这两种蛋白同时在转录起始点上被发现。rnTET2促进OGT在组蛋白H2B的O-GlcNAcylationrn反应(与活性基因相关的一个组蛋白标记)中rn的活性。因此，除了影响组蛋白修饰外，rnTET2还影响在转录调控中有潜在重要性的rnDNA修饰。%Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine and regulate gene transcription. However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive. Using protein affinity purification, here we search for functional partners of TET proteins, and find that TET2 and TET3 associate with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation) in vivo TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription start sites. Down-regulation of TET2 reduces the amount of histone 2B Serll2 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription.

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  • 来源
    《Nature》 |2013年第7433期|561-564a5|共5页
  • 作者

    Qiang Chen; Yibin Chen; Chunjing Bian; Ryoji Fujiki; Xiaochun Yu;

  • 作者单位

    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, 5560A MSRBII, Ann Arbor, Michigan 48109, USA;

    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, 5560A MSRBII, Ann Arbor, Michigan 48109, USA;

    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, 5560A MSRBII, Ann Arbor, Michigan 48109, USA;

    Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan,JST, PRESTO, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan;

    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, 5560A MSRBII, Ann Arbor, Michigan 48109, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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