TY - JOUR
T1 - Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes
AU - Yano, Seiichi
AU - Ishiuchi, Takashi
AU - Abe, Shusaku
AU - Namekawa, Satoshi H.
AU - Huang, Gang
AU - Ogawa, Yoshihiro
AU - Sasaki, Hiroyuki
N1 - Funding Information:
We thank K. Hayashi (Kyushu University) for sharing a confocal microscope and K. Shirane (Osaka University) for comments on the manuscript. We also thank the members of our laboratory, especially W.K. Au Yeung, J. Oishi, T. Hanagiri, and M. Miyake, and the common research facilities of the Medical Institute of Bioregulation, Kyushu University, for technical assistance. This work was supported by grants from a MEXT Grant-in-Aid for Scientific Research on Innovative Areas (JP19H05756 to T.I.); NIH grants (R35GM141085 to S.H.N.), (R01CA248019 and R01DK130478 to G.H.); and a JSPS Grant-in-Aid for Specially Promoted Research (JP18H05214 to H.S.).
Funding Information:
We thank K. Hayashi (Kyushu University) for sharing a confocal microscope and K. Shirane (Osaka University) for comments on the manuscript. We also thank the members of our laboratory, especially W.K. Au Yeung, J. Oishi, T. Hanagiri, and M. Miyake, and the common research facilities of the Medical Institute of Bioregulation, Kyushu University, for technical assistance. This work was supported by grants from a MEXT Grant-in-Aid for Scientific Research on Innovative Areas (JP19H05756 to T.I.); NIH grants (R35GM141085 to S.H.N.), (R01CA248019 and R01DK130478 to G.H.); and a JSPS Grant-in-Aid for Specially Promoted Research (JP18H05214 to H.S.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-32141-2
DO - 10.1038/s41467-022-32141-2
M3 - Article
C2 - 35922445
AN - SCOPUS:85135278204
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4440
ER -