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Chromatin targeting of de novo DNA methyltransferases by the PWWP domain
文献类型：期刊论文
| 作者 | Ge, YZ; Pu, MT; Gowher, H; Wu, HP; Ding, JP; Jeltsch, A; Xu, GL |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2004 |
| 卷号 | 279期号:24页码:25447-25454 |
| 通讯作者 | Xu, GL (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,glxu@sibs.ac.cn |
| 英文摘要 | DNA methylation patterns of mammalian genomes are generated in gametogenesis and early embryonic development. Two de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the process. Both enzymes contain a long N-terminal regulatory region linked to a conserved C-terminal domain responsible for the catalytic activity. Although a PWWP domain in the N-terminal region has been shown to bind DNA in vitro, it is unclear how the DNA methyltransferases access their substrate in chromatin in vivo. We show here that the two proteins are associated with chromatin including mitotic chromosomes in mammalian cells, and the PWWP domain is essential for the chromatin targeting of the enzymes. The functional significance of PWWP-mediated chromatin targeting is suggested by the fact that a missense mutation in this domain of human DNMT3B causes immunodeficiency, centromeric heterochromatin instability, facial anomalies (ICF) syndrome, which is characterized by loss of methylation in satellite DNA, pericentromeric instability, and immunodeficiency. We demonstrate that the mutant protein completely loses its chromatin targeting capacity. Our data establish the PWWP domain as a novel chromatin/chromosome-targeting module and suggest that the PWWP-mediated chromatin association is essential for the function of the de novo methyltransferases during development. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | HISTONE H3 METHYLTRANSFERASE ; ACUTE MYELOID-LEUKEMIA ; IMMUNODEFICIENCY SYNDROME ; MAMMALIAN DEVELOPMENT ; METHYLATION PATTERNS ; NEUROSPORA-CRASSA ; COACTIVATORS P52 ; ICF SYNDROME ; IN-VIVO ; DNMT3B |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000221827900068 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2181]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Ge, YZ,Pu, MT,Gowher, H,et al. Chromatin targeting of de novo DNA methyltransferases by the PWWP domain[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(24):25447-25454. |
| APA | Ge, YZ.,Pu, MT.,Gowher, H.,Wu, HP.,Ding, JP.,...&Xu, GL.(2004).Chromatin targeting of de novo DNA methyltransferases by the PWWP domain.JOURNAL OF BIOLOGICAL CHEMISTRY,279(24),25447-25454. |
| MLA | Ge, YZ,et al."Chromatin targeting of de novo DNA methyltransferases by the PWWP domain".JOURNAL OF BIOLOGICAL CHEMISTRY 279.24(2004):25447-25454. |
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