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小鼠卵母细胞减数分裂成熟过程中组蛋白H3苏氨酸3位点磷酸化的动力学

Dynamics of histone H3 phosphorylation at threonine 3 during meiotic maturation in mouse oocytes.

作者信息

Kang Hyoeun, Park Yong Seok, Cho Dong-Hyung, Kim Jae-Sung, Oh Jeong Su

机构信息

Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.

Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, South Korea.

出版信息

Biochem Biophys Res Commun. 2015 Mar 6;458(2):280-6. doi: 10.1016/j.bbrc.2015.01.099. Epub 2015 Jan 31.

Abstract

Various histone residues are post-translationally modified during the cell cycle. Among these, histone H3 phosphorylation at threonine 3 (H3T3ph) is newly characterized and has been considered to be crucial for chromosome dynamics during mitosis. However, little is known about the role of H3T3ph during mouse oocyte maturation. In the present study, we examined H3T3ph expression and localization during oocyte meiosis. Our results showed that H3T3ph was tightly associated with condensed chromosomes during meiotic maturation. H3T3ph along the chromosome arms was dissociated at anaphase/telophase I, but centromeric H3T3ph remained intact. Moreover, the inhibition of H3T3ph with the small molecule inhibitors CHR-6494 and 5-Itu impaired segregation of homologous chromosomes during meiosis. Partial inhibition of H3T3ph revealed that centromeric Aurora B/C kinase is sufficient to complete meiosis I, but Aurora B/C kinase along the chromosome arms is required to ensure accurate homologous chromosome segregation. Therefore, our results demonstrate that H3T3ph is a universal regulator of chromosome dynamics during oocyte meiosis and mitosis.

摘要

在细胞周期中,各种组蛋白残基会发生翻译后修饰。其中,苏氨酸3位点的组蛋白H3磷酸化(H3T3ph)是新发现的修饰,并且被认为对有丝分裂期间的染色体动态变化至关重要。然而,关于H3T3ph在小鼠卵母细胞成熟过程中的作用却知之甚少。在本研究中,我们检测了卵母细胞减数分裂过程中H3T3ph的表达和定位。我们的结果表明,在减数分裂成熟过程中,H3T3ph与浓缩的染色体紧密相关。染色体臂上的H3T3ph在后期/末期I解离,但着丝粒处的H3T3ph保持完整。此外,用小分子抑制剂CHR-6494和5-Itu抑制H3T3ph会损害减数分裂过程中同源染色体的分离。对H3T3ph的部分抑制表明,着丝粒处的极光激酶B/C足以完成减数分裂I,但染色体臂上的极光激酶B/C是确保同源染色体准确分离所必需的。因此,我们的结果表明,H3T3ph是卵母细胞减数分裂和有丝分裂期间染色体动态变化的通用调节因子。

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