图1 SETD2作用机制
H3K36me3修饰主要位于基因体（gene body）区域，与活性常染色质的转录相关，也涉及到其他生物学过程，包括可变剪接、剂量补偿、转录抑制、DNA修复和重组等[1]。NSD1, NSD2, NSD3, ASH1L, SETMAR, SMYD2, SETD3是H3K36发生单甲基化和二甲基化修饰的writer，SETD2是H3K36发生三甲基化修饰的writer，同时SETD2与RNA聚合酶II存在互作（图1）[1，3]。DNMT3是H3K36me3修饰的一个reader，H3K36me3能被DNMT3甲基化酶所包含的PWWP结构域识别，从而导致基因体区域的DNA甲基化增加（图2）[2]。剂量补偿体现在雄性果蝇物种中X染色体上的基因表达，通过MSL复合体保证了X连锁基因的表达水平与雌性果蝇(有两条X染色体)保持一致，具体途径是通过H3K36me3的修饰促进了基因的延伸，从而增加表达量[4]。
图2 H3K36me3介导DNA甲基化
参考文献
1、Wagner, Eric J., and Phillip B. Carpenter. "Understanding the language of Lys36 methylation at histone H3." Nature reviews Molecular cell biology 13, no. 2 (2012): 115-126.
2、Rondelet, Grégoire, Thomas Dal Maso, Luc Willems, and Johan Wouters. "Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B." Journal of structural biology 194, no. 3 (2016): 357-367.
3、Bannister, A. J. et al. Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J. Biol. Chem. 280, 17732–17736 (2005).
4、Larschan, E. et al. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila. Nature 471, 115–118 (2011).
