Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer

@inproceedings{Jia2016NegativeRO,
  title={Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer},
  author={Yuanhui Jia and Pishun Li and Lan Fang and Haijun Zhu and Liangliang Xu and Hao Cheng and Junying Zhang and Fei Li and Yan Feng and Yan Xiu Li and Jialun Li and Ruiping Wang and James X. Du and Jiwen Li and Taiping Chen and Hongbin Ji and Jackie Han and Wenqiang Yu and Qihan Wu and Jiemin Wong},
  booktitle={Cell Discovery},
  year={2016}
}
Global DNA hypomethylation is a most common epigenetic alteration in cancer, but the mechanism remains elusive. Previous studies demonstrate that UHRF1 but not UHRF2 is required for mediating DNA maintenance methylation by DNMT1. Here we report unexpectedly a conserved function for UHRF1 and UHRF2: inhibiting de novo DNA methylation by functioning as E3 ligases promoting DNMT3A degradation. UHRF1/2 are frequently overexpressed in cancers and we present evidence that UHRF1/2 overexpression… CONTINUE READING