DNA甲基化对卵泡刺激素受体表达的影响

Effect of DNA Methylation on Expression of Follicle-stimulating Hormone Receptor

DNA甲基化是广泛存在的可遗传的共价修饰方式。甲基化程度的增加通过以下4种途径抑制相应基因表达:①DNA甲基化直接抑制DNA结合蛋白与相应序列的结合。②DNA甲基化通过甲基化CpG结合蛋白抑制基因表达。③DNA甲基化转移酶直接参与基因沉默过程。④DNA甲基化影响基因转录的延伸过程。DNA甲基化对卵泡刺激素受体(FSHR)基因的细胞特异性表达也有调节作用,这一作用通过直接影响蛋白-DNA结合及甲基化CpG结合蛋白抑制基因表达这两种途径实现。综述DNA甲基化抑制基因表达的途径、FSHR转录调节及DNA甲基化对FSHR表达作用。

DNA methylation is a covalence and inheritable modification of DNA that does not alter the nucleotide sequence. Methylation is associated with repressed chromatin state and inhibition of gene expression. There are four general mechanisms by which DNA methylation inhibits gene expression. Firstly, DNA methylation of cytosine bases inhibits the binding of some DNA-binding factors with their cognate DNA recognition sequences. Secondly, methyl-CpG-binding proteins （MBPs） inhibit gene expression by silencing transcription. Thirdly, DNA methyhransferase enzymes themselves are involved in implementing the silenced state in addition to their catalytic activities. Fourthly, DNA methylation affects transcriptional elongation in addition to its characterized role in inhibiting transcriptional activation. DNA methylation is involved in regulating the tissue-specific expression of Follicle-stimulating hormone receptor （FSHR） gene by directly affecting the binding of required transcription factors with their cognate DNA recognition sequences, and in addition, by recruitment of MBPs. This review aims to summarize the routes to repression by DNA methylation and the effect of DNA methylation on expression of follicle- stimulating hormone receptor.