Xin Gu
Yu-Ting Liu
Zhen Zhou
Ling-Li Zhang
Yang Wen
Wei-Li Zhong
Guo-Liang Xu
Jin-Qiu Zhou
aState Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
bSchool of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
More InformationCorresponding author: E-mail address: jqzhou@sibcb.ac.cn (Jin-Qiu Zhou)
Publish Date:2020-02-25
Abstract
Abstract
A nucleosome contains two copies of each histone H2A, H2B, H3 and H4. Histone H3 K4me0 and K36me3 are two key chromatin marks forde novo DNA methylation catalyzed by DNA methyltransferases in mammals. However, it remains unclear whether K4me0 and K36me3 marks on both sister histone H3s regulate de novo DNA methylation independently or cooperatively. Here, taking advantage of the bivalent histone H3 system in yeast, we examined the contributions of K4 and K36 on sister histone H3s to genomic DNA methylation catalyzed by ectopically co-expressed murine Dnmt3a and Dnmt3L. The results show that lack of both K4me0 and K36me3 on one sister H3 tail, or lack of K4me0 and K36me3 on respective sister H3s results in a dramatic reduction of 5mC, revealing a synergy of two sister H3s in DNA methylation regulation. Accordingly, the Dnmt3a or Dnmt3L mutation that disrupts the interaction of Dnmt3aADD domain-H3K4me0, Dnmt3LADD domain-H3K4me0, or Dnmt3aPWWP domain-H3K36me3 causes a significant reduction of DNA methylation. These results support the model that each heterodimeric Dnmt3a-Dnmt3L reads both K4me0 and K36me3 marks on one tail of sister H3s, and the dimer of heterodimeric Dnmt3a-Dnmt3L recognizes two tails of sister histone H3s to efficiently execute de novo DNA methylation.Keywords: Asymmetrical nucleosome,
Histone H3K4 methylation,
Histone H3K36 methylation,
Yeast
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