DNA methyltransferases are complementary in maintaining DNA methylation in embryonic stem cells
Yuhan Liu, Zhen Xu, Jiajia Shi, Yu Zhang, Shuting Yang, Qian Chen, Chenglin Song, Shuhui Geng, Qing Li, Jinsong Li, Guoliang Xu, Wei Xie, Haodong Lin, Xiajun Li
Abstract
mutant ES cells, which could not be prevented by the elimination of three TET proteins. To elucidate methylation maintenance mechanisms, we generated mutant ES clones lacking three major DNA methyltransferases (DNMTs). Intriguingly, DNMT3A and DNMT3B were essential for DNA methylation at a subset of ICRs in mouse ES cells although DNMT1 maintained DNA methylation at most known ICRs. These were similarly observed after extended culture. Germline-derived DNA methylation was lost at the examined ICRs lacking DNMTs according to allelic analysis. Similar to DNMT1, DNMT3A and DNMT3B were required for maintaining DNA methylation at repeats, genic regions, and other genomic sequences. Therefore, three DNA methyltransferases play complementary roles in maintaining DNA methylation in mouse ES cells including DNA methylation at the ICRs primarily mediated through the ZFP57-dependent pathway.