TY - JOUR
T1 - Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes
AU - Hatanaka, Yuki
AU - Tsusaka, Takeshi
AU - Shimizu, Natsumi
AU - Morita, Kohtaro
AU - Suzuki, Takehiro
AU - Machida, Shinichi
AU - Satoh, Manabu
AU - Honda, Arata
AU - Hirose, Michiko
AU - Kamimura, Satoshi
AU - Ogonuki, Narumi
AU - Nakamura, Toshinobu
AU - Inoue, Kimiko
AU - Hosoi, Yoshihiko
AU - Dohmae, Naoshi
AU - Nakano, Toru
AU - Kurumizaka, Hitoshi
AU - Matsumoto, Kazuya
AU - Shinkai, Yoichi
AU - Ogura, Atsuo
PY - 2017/9/19
Y1 - 2017/9/19
N2 - At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a. Mettl23 interacts with Tet3, a 5mC-oxidizing enzyme responsible for active DNA demethylation, by binding to another maternal factor, GSE (gonad-specific expression). Depletion of Mettl23 from oocytes resulted in impaired accumulation of GSE, Tet3, and 5hmC in the male pronucleus, suggesting that Mettl23 may recruit GSE-Tet3 to chromatin. Our findings establish H3R17me2a and its catalyzing enzyme Mettl23 as key regulators of paternal genome reprogramming.
AB - At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a. Mettl23 interacts with Tet3, a 5mC-oxidizing enzyme responsible for active DNA demethylation, by binding to another maternal factor, GSE (gonad-specific expression). Depletion of Mettl23 from oocytes resulted in impaired accumulation of GSE, Tet3, and 5hmC in the male pronucleus, suggesting that Mettl23 may recruit GSE-Tet3 to chromatin. Our findings establish H3R17me2a and its catalyzing enzyme Mettl23 as key regulators of paternal genome reprogramming.
KW - active DNA demethylation
KW - fertilization
KW - histone arginine methylation
KW - histone variant
KW - zygotes
UR - http://www.scopus.com/inward/record.url?scp=85029587722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029587722&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.08.088
DO - 10.1016/j.celrep.2017.08.088
M3 - Article
AN - SCOPUS:85029587722
SN - 2211-1247
VL - 20
SP - 2756
EP - 2765
JO - Cell Reports
JF - Cell Reports
IS - 12
ER -