Aging-associated reduction of chromosomal histones in mammalian oocytes

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-23 DOI:10.1111/gtc.13146

Masashi Mori, Manami Koshiguchi, Osamu Takenouchi, Mei A. Mukose, Hinako M. Takase, Tappei Mishina, Hailiang Mei, Miho Kihara, Takaya Abe, Azusa Inoue, Tomoya S. Kitajima

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Abstract

Mammalian oocytes undergo a long-term meiotic arrest that can last for almost the entire reproductive lifespan. This arrest occurs after DNA replication and is prolonged with age, which poses a challenge to oocytes in maintaining replication-dependent chromosomal proteins required for the completion of meiosis. In this study, we show that chromosomal histones are reduced with age in mouse oocytes. Both types of histone H3 variants, replication-dependent H3.1/H3.2 and replication-independent H3.3, decrease with age. Aging-associated histone reduction is associated with transcriptomic features that are caused by genetic depletion of histone H3.3. Neither the genetic reduction of chromosomal H3.1/H3.2 nor H3.3 accelerates the aging-associated increase in premature chromosome separation that causes meiotic segregation errors. We suggest that aging-associated reduction of chromosomal histones is linked to several transcriptomic abnormalities but does not significantly contribute to errors in meiotic chromosome segregation during the reproductive lifespan of mice.

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哺乳动物卵母细胞中与衰老相关的染色体组蛋白减少。

哺乳动物的卵母细胞会经历长期的减数分裂停滞，这种停滞几乎会持续整个生殖寿命。这种停滞发生在 DNA 复制之后，并随着年龄的增长而延长，这给卵母细胞维持完成减数分裂所需的依赖复制的染色体蛋白带来了挑战。在这项研究中，我们发现小鼠卵母细胞中的染色体组蛋白会随着年龄的增长而减少。两种类型的组蛋白 H3 变体（依赖复制的 H3.1/H3.2 和不依赖复制的 H3.3）都会随着年龄的增长而减少。与衰老相关的组蛋白减少与组蛋白 H3.3 遗传耗竭引起的转录组特征有关。染色体 H3.1/H3.2 或 H3.3 的遗传减少都不会加速与衰老相关的染色体过早分离的增加，而过早分离会导致减数分裂错误。我们认为，与衰老相关的染色体组蛋白减少与几种转录组异常有关，但对小鼠生殖寿命期间减数分裂染色体分离错误并无显著影响。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.