Elucidation of paternal genome reprogramming in mammalian zygotes

September 20, 2017

Discovery of a necessary histone methylation

A joint research group comprised of the RIKEN BioResource Center, the Cellular Memory Laboratory (a RIKEN Chief Scientist Laboratory), RIKEN CSRS and others have discovered a new regulatory mechanism for the reprogramming of the mammalian sperm genome at the time of fertilization using a mouse model.

The collaborative research group newly identified that the maternal (ova-derived) factor Mettl23 is involved in reprogramming the sperm genome. Biochemical analysis revealed that Mettl23 is an arginine methyltransferase that catalyzes asymmetric dimethylation of the tail end of Histone H3 at arginine 17 (H3R17me2a). Researchers also found that this H3R17me2a is essential for the uptake of Histone H3.3 into the sperm genome.

Furthermore, observation of Mettl23-deficient mice created with genomic editing techniques revealed that Mettl23 is indispensable for the binding of active DNA demethlyation factor GSE and the Tet3 enzyme to the sperm genome. These findings made clear that the histone-modifying enzyme Mettl23 and the histone dimethylation–modified H3R17me2a that catalyzes Mettl23 play an important role in the reprogramming process of the paternal genome play through protamine-histone exchange and active DNA demethylation.

This research is expected to further progress understanding of the mechanisms of totipotency acquisition. Moreover, if the effects of the identified factors on establishing and maintaining pluripotency can be confirmed, there are potential applications in the field of regenerative medicine.


Original article
Cell Reports doi:10.1016/j.celrep.2017.08.088
Y. Hatanaka, T. Tsusaka, N. Shimizu, K. Morita, T. Suzuki, S. Machida, M. Satoh, A. Honda, M. Hirose, S. Kamimura, N. Ogonuki, T. Nakamura, K. Inoue, Y. Hosoi, N. Dohmae, T. Nakano, H. Kurumizaka, K. Matsumoto, Y. Shinkai, A. Ogura,
"Histone H3 methylated at arginine 17 is essential for reprogramming the paternal genome in zygotes".

Naoshi Dohmae
Unit Leader
Biomolecular Characterization Unit