Year: 2024
Type: article
Abstract: In mammals, global passive demethylation contributes to epigenetic reprogramming during early embryonic development. At this stage, the majority of DNA-methyltransferase 1 (DNMT1) protein is excluded from nucleus, which is considered the primary cause. However, whether the remaining nuclear activity of DNMT1 is regulated by additional mechanisms is unclear. Here, we report that nuclear DNMT1 abundance is finetuned through proteasomal degradation in mouse zygotes. We identify a maternal factor, Pramel15, which targets DNMT1 for degradation via Cullin-RING E3 ligases. Loss of Pramel15 elevates DNMT1 levels in the zygote pronuclei, impairs zygotic DNA demethylation, and causes a stochastic gain of DNA methylation in early embryos. Thus, Pramel15 can modulate the residual level of DNMT1 in the nucleus during zygotic DNA replication, thereby ensuring efficient DNA methylation reprogramming in early embryos. Epigenetic reprogramming involves global loss of DNA methylation, but how this is regulated is not completely understood. Here, Tan et al. run a reverse genetic screen and report that nuclear DNMT1 is finetuned by maternal factor Pramel15 through proteasomal degradation in mouse zygotes.
Source: Nature Communications
Authors: Jiajun Tan, Yingfeng Li, Xiang Li, Xiaoxiao Zhu, Liping Liu, Hua Huang, Jiahua Wei, Hailing Wang, Yong Tian, Zhigao Wang, Zhuqiang Zhang, Bing Zhu
Institutions: Chinese Academy of Sciences, Institute of Biophysics, University of Chinese Academy of Sciences, The University of Texas Southwestern Medical Center, Research Center for Eco-Environmental Sciences, State Key Laboratory of Environmental Chemistry and Ecotoxicology, University of South Florida
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
OpenAlex ID: W4401865145