Migeon B R, Holland M M, Driscoll D J, Robinson J C
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Somat Cell Mol Genet. 1991 Mar;17(2):159-68. doi: 10.1007/BF01232973.
The mechanism for establishing the DNA methylation patterns observed in adult mammalian tissues is not well understood. To determine when adult patterns are established for housekeeping genes, we examined the clustered CpGs in genes on the human active X chromosome (PGK, G6PD, P3, GdX, HPRT) and the autosomal gene, DHFR. We find unique methylation patterns present at the P3 locus in all tissues analyzed from 6- to 9-week fetal specimens, and at the HPRT locus in adrenal gland DNA at this stage of development. Adult patterns are established subsequently by demethylating specific CpGs. Our results show that demethylating events affecting CpG islands are programmed during mammalian fetal development. They suggest that the process of de novo methylation in the fetus methylates at least some sites in the 3' region of the CpG islands in active genes and that adult patterns are established at 6-14 weeks developmental age by sequence-specific demethylation.
目前人们对在成年哺乳动物组织中观察到的DNA甲基化模式的建立机制还了解甚少。为了确定管家基因的成年模式何时建立，我们检测了人类活性X染色体上基因（PGK、G6PD、P3、GdX、HPRT）以及常染色体基因DHFR中的成簇CpG。我们发现在6至9周龄胎儿标本的所有分析组织中，P3位点存在独特的甲基化模式，在发育的这个阶段，肾上腺DNA中的HPRT位点也存在独特的甲基化模式。随后通过对特定CpG进行去甲基化来建立成年模式。我们的结果表明，影响CpG岛的去甲基化事件在哺乳动物胎儿发育过程中是程序性的。这些结果表明，胎儿中的从头甲基化过程使活性基因中CpG岛3'区域的至少一些位点发生甲基化，并且成年模式在发育年龄6至14周时通过序列特异性去甲基化而建立。
