Jones P L, Veenstra G J, Wade P A, Vermaak D, Kass S U, Landsberger N, Strouboulis J, Wolffe A P
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-5431, USA.
Nat Genet. 1998 Jun;19(2):187-91. doi: 10.1038/561.
CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.
脊椎动物中的CpG甲基化与染色质结构改变和基因沉默相关。DNA甲基化状态的差异与印记现象和致癌作用有关。在非洲爪蟾卵母细胞中，DNA甲基化主要通过组装抑制性核小体阵列使转录沉默。组装到染色质中的甲基化DNA结合转录抑制因子MeCP2，MeCP2与Sin3和组蛋白去乙酰化酶共分离。抑制组蛋白去乙酰化酶可解除MeCP2和甲基化DNA介导的沉默，促进染色质重塑和转录激活。这些结果确立了DNA甲基化依赖性转录沉默与染色质修饰之间的直接因果关系。
