Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
Trends Genet. 2015 May;31(5):274-80. doi: 10.1016/j.tig.2015.03.002. Epub 2015 Mar 30.
Although DNA methylation was originally thought to only affect transcription, emerging evidence shows that it also regulates alternative splicing. Exons, and especially splice sites, have higher levels of DNA methylation than flanking introns, and the splicing of about 22% of alternative exons is regulated by DNA methylation. Two different mechanisms convey DNA methylation information into the regulation of alternative splicing. The first involves modulation of the elongation rate of RNA polymerase II (Pol II) by CCCTC-binding factor (CTCF) and methyl-CpG binding protein 2 (MeCP2); the second involves the formation of a protein bridge by heterochromatin protein 1 (HP1) that recruits splicing factors onto transcribed alternative exons. These two mechanisms, however, regulate only a fraction of such events, implying that more underlying mechanisms remain to be found.
尽管最初认为 DNA 甲基化仅影响转录，但新出现的证据表明它也调节选择性剪接。外显子，尤其是剪接位点，比侧翼内含子具有更高水平的 DNA 甲基化，并且约 22%的选择性外显子的剪接受 DNA 甲基化调控。两种不同的机制将 DNA 甲基化信息传递到选择性剪接的调节中。第一种机制涉及 CCCTC 结合因子 (CTCF) 和甲基化-CpG 结合蛋白 2 (MeCP2) 调节 RNA 聚合酶 II (Pol II) 的延伸率；第二种机制涉及异染色质蛋白 1 (HP1) 形成蛋白质桥，将剪接因子募集到转录的选择性外显子上。然而，这两种机制仅调节这些事件的一部分，这意味着仍然存在更多潜在的机制。
