De novo methylation of an embryonic globin gene during normal development is strand specific and spreads from the proximal transcribed region
De novo methylation of an embryonic globin gene during normal development is strand specific and spreads from the proximal transcribed region
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DOI：
10.1182/blood.v98.12.3441
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发表时间：
2001-12-01
期刊：
影响因子：
20.3
通讯作者：
vanWert, JM
中科院分区：
文献类型：
--
作者：
Singal, R;vanWert, JM
最近发现的从头甲基转移酶DNMT 3a和DNMT 3b已被证明对胚胎发育至关重要。然而，在单个基因水平上，对甲基化模式在发育过程中如何建立知之甚少。禽胚胎β-珠蛋白基因启动子在4天大的鸡胚胎红系细胞中完全未甲基化，在那里它以高水平表达，并且在成年红系细胞中完全甲基化，在那里它是沉默的。在鸡红系细胞发育过程中，研究了β-珠蛋白基因启动子、近端转录区和远端转录区的甲基化模式。发现从头甲基化最初靶向编码（顶部）链上的CpG密集近端转录区，随后扩散到3'区和启动子区。模板（底部）链的甲基化滞后于编码链的甲基化，两条链的完全甲基化只有在基因沉默后才发生。研究结果表明，从头甲基化模式的建立涉及链特异性和甲基化扩散。（血。2001;98：3441-3446）（C）2001由美国血液学学会。
The recently discovered de novo methyltransferases DNMT3a and DNMT3b have been shown to be critical to embryonic development. However, at a single gene level, little is known about how the methylation pattern is established during development. The avian embryonic p-globin gene promoter is completely unmethylated in 4-day-old chicken embryonic erythroid cells, where it is expressed at a high level, and completely methylated in adult erythroid cells, where it is silent. The methylation pattern of the p-globin gene promoter, proximal transcribed region, and distal transcribed region on both DNA strands was examined during development in chicken erythroid cells. It was found that de novo methylation targets the CpG-dense proximal transcribed region on the coding (top) strand initially, followed by spreading into the 3' region and into the promoter region. Methylation of the template (bottom) strand lags behind that of the coding strand, and complete methylation of both strands occurs only after the gene has been silenced. The results of the study indicate that establishment of the de novo methylation pattern involves strand-specificity and methylation spreading. (Blood. 2001;98: 3441-3446) (C) 2001 by The American Society of Hematology.