Sullivan C H, Grainger R M
Proc Natl Acad Sci U S A. 1987 Jan;84(2):329-33. doi: 10.1073/pnas.84.2.329.
Although it has been argued that the loss of 5-methylcytosine from specific sites in DNA plays an important role in activation of specific genes, the mechanism of hypomethylation is not well understood. One model links the process to DNA replication, proposing that it occurs by not remethylating cytosine on newly synthesized DNA. An alternative model argues that hypomethylation results from excision of part or all of the 5-methylcytosine. We were able to test whether hypomethylation can occur without replication by analysis of methylation changes in the delta-crystallin genes of the chicken lens. During embryonic development a large fraction of cells in the lens stops dividing as part of the differentiation process. Shortly after this stage, the delta-crystallin genes in samples of the whole lens become hypomethylated, suggesting the possibility that this process might be occurring in the subset of cells that is no longer dividing. We found that hypomethylation of these genes does occur in postmitotic lens cells, a result that implicates an excision mechanism in this tissue.
尽管有人认为DNA特定位点上5-甲基胞嘧啶的缺失在特定基因的激活中起重要作用，但低甲基化的机制尚未完全了解。一种模型将该过程与DNA复制联系起来，提出它是通过不对新合成的DNA上的胞嘧啶进行重新甲基化而发生的。另一种模型则认为低甲基化是由部分或全部5-甲基胞嘧啶的切除导致的。我们能够通过分析鸡晶状体δ-晶体蛋白基因的甲基化变化来测试低甲基化是否可以在没有复制的情况下发生。在胚胎发育过程中，晶状体中的大部分细胞作为分化过程的一部分停止分裂。在这个阶段之后不久，整个晶状体样本中的δ-晶体蛋白基因就会发生低甲基化，这表明这个过程可能发生在不再分裂的细胞亚群中。我们发现这些基因的低甲基化确实发生在有丝分裂后的晶状体细胞中，这一结果表明该组织中存在切除机制。
