Hada Masashi, Kim Jihye, Inoue Erina, Fukuda Yuko, Tanaka Hiromitsu, Watanabe Yoshinori, Okada Yuki
Laboratory of Pathology and Development, The University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-0032, Japan.
Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-0032, Japan.
Chromosoma. 2017 Dec;126(6):769-780. doi: 10.1007/s00412-017-0638-5. Epub 2017 Aug 12.
Histone phosphorylation is sometimes associated with mitosis and meiosis. We have recently identified a phosphorylation of the 127th threonine on TH2A (pTH2A), a germ cell-specific H2A variant, in condensed spermatids and mitotic early preimplantation embryos of mice. Here, we further report the existence of pTH2A at the centromeres in metaphase I spermatocytes and oocytes. Moreover, we identified Haspin, a known kinase for the 3rd threonine on H3, is responsible for pTH2A in vivo. In contrast to the severe meiotic defect in oocytes treated with a Haspin inhibitor, pTH2A-deficient mice, in which the 127th threonine was replaced by alanine, maintained the fertility and exhibited no obvious defect in both oocytes and spermatogenesis. Interestingly, pTH2A was significantly decreased in aged oocytes, suggesting that its accumulation is regulated by centromeric cohesins. Collectively, our study proposes a new set of kinase-histone pair at meiotic centromere, which is highly coordinated during meiosis.
组蛋白磷酸化有时与有丝分裂和减数分裂相关。我们最近在小鼠的浓缩精子细胞和有丝分裂早期着床前胚胎中,发现了生殖细胞特异性H2A变体TH2A上第127位苏氨酸的磷酸化(pTH2A)。在此,我们进一步报道在减数第一次分裂中期的精母细胞和卵母细胞的着丝粒处存在pTH2A。此外,我们确定已知的H3第3位苏氨酸的激酶Haspin在体内负责pTH2A的产生。与用Haspin抑制剂处理的卵母细胞中严重的减数分裂缺陷相反,第127位苏氨酸被丙氨酸取代的pTH2A缺陷小鼠保持了生育能力,并且在卵母细胞和精子发生过程中均未表现出明显缺陷。有趣的是,pTH2A在老化的卵母细胞中显著减少,这表明其积累受着丝粒黏连蛋白调节。总的来说,我们的研究提出了一组新的减数分裂着丝粒处的激酶 - 组蛋白对,其在减数分裂过程中高度协调。