Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L
文献类型：期刊论文
| 作者 | Xie, ZH; Huang, YN; Chen, ZX; Riggs, AD; Ding, JP; Gowher, H; Jeltsch, A; Sasaki, H; Hata, K; Xu, GL |
| 刊名 | HUMAN MOLECULAR GENETICS
 |
| 出版日期 | 2006 |
| 卷号 | 15期号:9页码:1375-1385 |
| 通讯作者 | Xu, GL (reprint author), Chinese Acad Sci, Shanghai Inst Biol 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 | Deficiency in DNA methyltransferase DNMT3B causes a recessive human disorder characterized by immunodeficiency, centromeric instability and facial anomalies (ICF) in association with defects in genomic methylation. The majority of ICF mutations are single amino acid substitutions in the conserved catalytic domain of DNMT3B, which are believed to impair its enzymatic activity directly. The establishment of intact genomic methylation patterns in development requires a fine regulation of the de novo methylation activity of the two related methyltransferases DNMT3A and DNMT3B by regulatory factors including DNMT3L which has a stimulatory effect. Here, we show that two DNMT3B mutant proteins with ICF-causing substitution (A766P and R840Q) displayed a methylation activity similar to the wild-type enzyme both in vitro and in vivo. However, their stimulation by DNMT3L was severely compromised due to deficient protein interaction. Our findings suggest that methylation defects in ICF syndrome may also result from impaired stimulation of DNMT3B activity by DNMT3L or other unknown regulatory factors as well as from a weakened basal catalytic activity of the mutant DNMT3B protein per se. |
| 学科主题 | Biochemistry & Molecular Biology; Genetics & Heredity |
| 类目[WOS] | Biochemistry & Molecular Biology ; Genetics & Heredity |
| 关键词[WOS] | DE-NOVO METHYLATION ; IMMUNODEFICIENCY SYNDROME ; PREIMPLANTATION EMBRYOS ; MAMMALIAN DEVELOPMENT ; GERM-LINE ; EXPRESSION ; CELLS ; GENE ; HETEROCHROMATIN ; IMPRINTS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000237002400001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1764]  |
| 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 | Xie, ZH,Huang, YN,Chen, ZX,et al. Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L[J]. HUMAN MOLECULAR GENETICS,2006,15(9):1375-1385. |
| APA | Xie, ZH.,Huang, YN.,Chen, ZX.,Riggs, AD.,Ding, JP.,...&Xu, GL.(2006).Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L.HUMAN MOLECULAR GENETICS,15(9),1375-1385. |
| MLA | Xie, ZH,et al."Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L".HUMAN MOLECULAR GENETICS 15.9(2006):1375-1385. |
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