Ng H H, Bird A
Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3JR, UK.
Curr Opin Genet Dev. 1999 Apr;9(2):158-63. doi: 10.1016/s0959-437x(99)80024-0.
DNA methylation and chromatin modification are two global mechanisms that regulate gene expression. Recent studies provide insight into the mechanism of transcriptional silencing by a methyl-CpG binding protein, MeCP2. MeCP2 is shown to interact with the Sin3/histone deacetylase co-repressor complex. Thus, this interaction can provide a mechanistic explanation for the long-known relationship between DNA methylation and chromatin structure. Moreover, several studies have shown that inhibition of histone deacetylases by specific inhibitors can reactivate endogenous genes or reporter constructs previously silenced by DNA methylation. Taken together, the data strongly suggest that DNA methylation can pattern chromatin modification.
DNA甲基化和染色质修饰是两种调节基因表达的整体机制。最近的研究深入探讨了甲基化CpG结合蛋白MeCP2介导的转录沉默机制。研究表明,MeCP2与Sin3/组蛋白去乙酰化酶共抑制复合物相互作用。因此,这种相互作用能够为DNA甲基化与染色质结构之间长期以来已知的关系提供一种机制性解释。此外,多项研究表明,用特定抑制剂抑制组蛋白去乙酰化酶能够重新激活内源性基因或先前因DNA甲基化而沉默的报告基因构建体。综上所述,这些数据有力地表明,DNA甲基化能够调控染色质修饰。