DNMT3A reads and connects histone H3K36me2 to DNA methylation

作者：Wenqi Xu, Jiahui Li, Bowen Rong, Bin Zhao, Mei Wang, Ruofei Dai, Qilong Chen, Hang Liu, Zhongkai Gu, Shuxian Liu, Rui Guo, Hongjie Shen, Feizhen Wu, Fei Lan · 发表于：Protein & Cell · 年份：2019 · DOI：10.1007/s13238-019-00672-y · 被引用次数：52 · 研究领域：Epigenetics and DNA Methylation、RNA modifications and cancer、Cancer-related gene regulation

Dear Editor, DNA methylation at the 5-position of cytosine (5mC) is a crucial epigenetic mark in regulating biological processes including gene silencing, gene imprinting, and X chromosome inactivation (Jaenisch and Bird, 2003; Smith and Meissner, 2013). Human genome encodes three DNA methyltransferases, DNMT1, DNMT3A and DNMT3B to catalyze 5mC. Although not tightly restricted, DNMT1 is thought to maintain the established pattern of 5mC throughout DNA replication, while DNMT3A and DNMT3B are largely responsible for the de novo establishment of 5mC. It has long been questioned how de novo DNA 5mC patterns are established in different genomic regions and whether histone modifications crosstalk to the process. Until recently, it was reported that through recognition of histone H3K36me3 mark, DNMT3B plays a dominant role in mediating DNA 5mC in the genic region undergoing active transcription (Baubec et al., 2015; Neri et al., 2017). However, 5mC occurs at both intergenic and genic regions, while H3K36me3 is largely absent in the intergenic regions, indicating that the intergenic 5mC may be mediated through different mechanisms. Although H3K36me3 is involved in the DNMT3B mediated DNA 5mC in the genic regions (Baubec et al., 2015; Neri et al., 2017), we found that SETD2 loss in HEK293T cells did not cause reduction of global 5mC level, which was actually moderately increased by around 20% (Fig. S1A, left and middle), indicating alternative mechanism in directing DNA 5mC by histon...