Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis
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DOI:
10.1016/j.celrep.2016.12.065
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发表时间:
2017-01-17
期刊:
影响因子:
8.8
通讯作者:
Yamagata, Kazuo
Yamagata, Kazuo
中科院分区:
生物学1区
文献类型:
--
作者:
Ueda, Jun;Harada, Akihito;Yamagata, Kazuo

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细胞分化与动态染色质重塑相关,以建立细胞类型特异性表观基因组景观。在这里,我们发现,小鼠睾丸特异性和复制依赖性组蛋白H3变异H3t是必不可少的精子发生的非常早期的阶段。H3t基因缺陷导致无精子症,因为单倍体生殖细胞的损失。在正常精子发生过程中,当出现分化的精原细胞时,H3t出现并取代经典的H3蛋白。结构和生化分析表明,含H3t的核小体比典型的核小体更灵活。因此,通过在精原细胞分化期间将H3t并入基因组中,雄性生殖细胞能够进入减数分裂及以后。
Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-typespecific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.