DATE2025.06.09 #Press Releases

Discovery of a New Role for Histone Modification in Maintaining Chromosomal Integrity in Oocytes

~H3K4me3 Regulates the Stability of Oocyte Chromosomes and the Spindle~

Summary

Accurate chromosome segregation is essential for normal embryonic development following fertilization of an oocyte (egg cell). Abnormalities in this process are known to be a cause of infertility and miscarriage. In mature oocytes (at the metaphase II or MII stage), multiple mechanisms are in place to ensure proper chromosomal function. One such mechanism involves chemical modifications of histone proteins that package the chromosomes. Among these, the histone modification H3K4me3 is well known for its role in transcriptional activation. However, even in MII oocytes where transcription is inactive, H3K4me3 is abundantly present on chromosomes.

This study is the first in the world to reveal that, in mature oocytes, H3K4me3 plays a novel role distinct from transcriptional regulation—specifically, it is essential for maintaining the stability of both chromosomes and the spindle apparatus.

The research was conducted by a collaborative group including Professor Kei Miyamoto’s team at the Faculty of Agriculture, Kyushu University; graduate student Atsushi Takasu, Professor Kazuo Yamagata, and Professor Kazuya Matsumoto at the Graduate School of Biology-Oriented Science and Technology, Kindai University; Associate Professor Toshiaki Hino at the Faculty of Medicine, Asahikawa Medical University; Team Leader Tomoya S Kitajima at the RIKEN Center for Biosystems Dynamics Research; Professor Miho Ohsugi at the School of Science, The University of Tokyo; and Director Atsuo Ogura at the RIKEN BioResource Research Center. The team discovered that in mouse mature oocytes, H3K4me3 accumulates asymmetrically on the cortex side (near the cell membrane) of chromosomes (Figure). Furthermore, when H3K4me3 was artificially removed from the oocyte chromosomes, the spindle structure—which is responsible for aligning the chromosomes—became destabilized, resulting in a significant decrease in the oocyte’s ability to develop into a normal embryo after fertilization. The study also reports that in aged oocytes, H3K4me3 levels abnormally decline.

This groundbreaking discovery not only uncovers a new function of the extensively studied H3K4me3 modification but also holds promise as a molecular target for infertility treatment and miscarriage prevention. It opens a new avenue for understanding and potentially treating abnormalities in chromosome segregation in oocytes.

The findings of this research were published online in the American scientific journal Journal of Biological Chemistry on Thursday, May 29, 2025.

Figure: Schematic illustration of the study

Related Links

Kyushu University, Kindai University, Asahikawa Medical University, RIKEN

Published Journals

Journal Title	Journal of Biological Chemistry
Title	Characterization of H3K4me3 in mouse oocytes at the metaphase II stage