Abstract

Establishment of the DNA methylation landscape of mammalian oocytes, mediated by the DNMT3A-DNMT3L complex, is crucial for reproduction and development. In mouse oocytes, high levels of DNA methylation occur exclusively in the transcriptionally active regions, with moderate to low levels of methylation in other regions. Histone H3K36me3 mediates the high levels of methylation in the transcribed regions; however, it is unknown which histone mark guides the methylation in the other regions. Here, we show that, in mouse oocytes, H3K36me2 is highly enriched in the X chromosome and is broadly distributed across all autosomes. Upon H3K36me2 depletion, DNA methylation in moderately methylated regions is selectively affected, and a methylation pattern unique to the X chromosome is switched to an autosome-like pattern. Furthermore, we find that simultaneous depletion of H3K36me2 and H3K36me3 results in global hypomethylation, comparable to that of DNMT3A depletion. Therefore, the two histone marks jointly provide the chromatin platform essential for guiding DNMT3A-dependent DNA methylation in mouse oocytes.

DNMT3A is known to methylate DNA at histone H3 lysine 36 (H3K36me3)-marked transcriptionally active regions in mouse oocytes. Here the authors show that DNMT3A is also guided by H3K36me2 to methylate broad domains in genic and intergenic loci, as well as on the X chromosome. These two histone marks together comprise the minimal chromatin signature for global DNA methylation in mouse oocytes.

Details

Title
Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes
Author
Yano, Seiichi 1   VIAFID ORCID Logo  ; Ishiuchi, Takashi 2   VIAFID ORCID Logo  ; Abe, Shusaku 3 ; Namekawa, Satoshi H. 4   VIAFID ORCID Logo  ; Huang, Gang 5 ; Ogawa, Yoshihiro 6 ; Sasaki, Hiroyuki 3   VIAFID ORCID Logo 

1  Kyushu University, Division of Epigenomics and Development, Medical Institute of Bioregulation, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849); Kyushu University, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
2  Kyushu University, Division of Epigenomics and Development, Medical Institute of Bioregulation, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849); University of Yamanashi, Faculty of Life and Environmental Sciences, Yamanashi, Japan (GRID:grid.267500.6) (ISNI:0000 0001 0291 3581) 
3  Kyushu University, Division of Epigenomics and Development, Medical Institute of Bioregulation, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
4  University of California Davis, Department of Microbiology & Molecular Genetics, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
5  UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Department of Cell Systems & Anatomy and Department of Pathology & Laboratory Medicine, San Antonio, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X) 
6  Kyushu University, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-32141-2
ProQuest document ID
2697534979
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.