Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase
文献类型：期刊论文
| 作者 | Li, BZ; Huang, Z; Cui, QY; Song, XH; Du, L; Jeltsch, A; Chen, P; Li, GH; Li, E; Xu, GL |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 21期号:8页码:1172-1181 |
| 关键词 | de novo DNA methylation Dnmt3a Histone H3 tail PHD domain allosteric stimulation |
| 通讯作者 | Xu, GL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,glxu@sibs.ac.cn |
| 英文摘要 | Cytosine methylation of genomic DNA controls gene expression and maintains genome stability. How a specific DNA sequence is targeted for methylation by a methyltransferase is largely unknown. Here, we show that histone H3 tails lacking lysine 4 (K4) methylation function as an allosteric activator for methyltransferase Dnmt3a by binding to its plant homeodomain (PHD). In vitro, histone H3 peptides stimulated the methylation activity of Dnmt3a up to 8-fold, in a manner reversely correlated with the level of K4 methylation. The biological significance of allosteric regulation was manifested by molecular modeling and identification of key residues in both the PHD and the catalytic domain of Dnmt3a whose mutations impaired the stimulation of methylation activity by H3 peptides but not the binding of H3 peptides. Significantly, these mutant Dnmt3a proteins were almost inactive in DNA methylation when expressed in mouse embryonic stem cells while their recruitment to genomic targets was unaltered. We therefore propose a two-step mechanism for de novo DNA methylation - first recruitment of the methyltransferase probably assisted by a chromatin-or DNA-binding factor, and then allosteric activation depending on the interaction between Dnmt3a and the histone tails - the latter might serve as a checkpoint for the methylation activity. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | EMBRYONIC STEM-CELLS ; MAJOR SATELLITE REPEATS ; PWWP DOMAIN ; PERICENTRIC HETEROCHROMATIN ; MAMMALIAN DEVELOPMENT ; DNMT3A ; CHROMATIN ; GENOME ; H3 ; PATTERNS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000293341100005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/839]  |
| 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 | Li, BZ,Huang, Z,Cui, QY,et al. Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase[J]. CELL RESEARCH,2011,21(8):1172-1181. |
| APA | Li, BZ.,Huang, Z.,Cui, QY.,Song, XH.,Du, L.,...&Xu, GL.(2011).Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase.CELL RESEARCH,21(8),1172-1181. |
| MLA | Li, BZ,et al."Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase".CELL RESEARCH 21.8(2011):1172-1181. |
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