Bestor T H, Gundersen G, Kolstø A B, Prydz H
Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, MA 02115.
Genet Anal Tech Appl. 1992 Apr;9(2):48-53. doi: 10.1016/1050-3862(92)90030-9.
The CpG islands found at the 5' ends of many mammalian genes are typically unmethylated despite being both exposed to diffusible protein factors in nuclei and rich in CpG, the target site for DNA methyltransferase. We show here that the CpG islands associated with the human Thy-1 and profilin genes are inherently resistant to de novo methylation by purified murine DNA methyltransferase, and that the higher than expected tendency of CpG sites in islands to be flanked on both sides by G-C base pairs is the likely reason for the resistance. Several lines of evidence indicate that DNA methyltransferase does not make base-specific contacts with residues that flank CpG sites, and it is likely that CpG sites within islands are resistant to de novo methylation because of local conformational features such as ease of strand separation, minor groove dimensions, and alternative secondary structures. A role for minor groove contacts is consistent with the presence within a putative regulatory domain of numerous modified beta turn structural elements that can make minor groove contacts.
许多哺乳动物基因5'端的CpG岛通常是未甲基化的，尽管它们既暴露于细胞核中的可扩散蛋白质因子中，又富含作为DNA甲基转移酶靶位点的CpG。我们在此表明，与人类Thy-1和原肌球蛋白基因相关的CpG岛对纯化的鼠DNA甲基转移酶的从头甲基化具有内在抗性，并且岛内CpG位点两侧比预期更高的G-C碱基对侧翼倾向是产生抗性的可能原因。几条证据表明，DNA甲基转移酶不会与CpG位点侧翼的残基进行碱基特异性接触，并且岛内的CpG位点可能由于局部构象特征（如链分离的难易程度、小沟尺寸和替代二级结构）而对从头甲基化具有抗性。小沟接触的作用与众多可进行小沟接触的修饰β转角结构元件在假定调节域内的存在相一致。
