Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis

Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis
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DOI:
10.1073/pnas.0406060102
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发表时间:
2005-02-22
影响因子:
11.1
通讯作者:
Davidson, I
Davidson, I
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Martianov, I;Brancorsini, S;Davidson, I

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精子发生需要一个主要的生化和形态学的生殖细胞重组,包括体细胞组蛋白的替代鱼精蛋白包装的DNA到凝聚的精子!细胞核和细胞质的消除在伸长阶段。我们描述了H1 T2,组蛋白H1的变异选择性和瞬时表达的男性单倍体生殖细胞精子发生过程中。在圆形和伸长的精子细胞中,H1 T2特异性地定位于顶极的染色质结构域,揭示了精子细胞中的极性。原子核同源重组灭活表明,H1 T2是精子发生的关键,因为雄性HR 2(-/-)小鼠的生育能力大大降低。对H1 t2突变小鼠精子发生的分析显示,核凝聚延迟和异常延长。因此,突变精子细胞的特征是存在残留的细胞质、顶体脱离和DNA片段。因此,H1 T2是在精子发生的延伸阶段期间适当的细胞重组和DNA浓缩所需的蛋白质。
Spermiogenesis entails a major biochemical and morphological restructuring of the germ cell involving replacement of the somatic histones by protamines packing the DNA into the condensed spermatic! nucleus and elimination of the cytoplasm during the elongation phase. We describe H1T2, an histone H1 variant selectively and transiently expressed in male haploid germ cells during spermiogenesis. in round and elongating spermatids, H1T2 specifically localizes to a chromatin domain at the apical pole, revealing a polarity in the spermatic! nucleus. Inactivation by homologous recombination shows that H1T2 is critical for spermiogenesis as male HR2(-/-) mice have greatly reduced fertility. Analysis of spermiogenesis in H1t2 mutant mice shows delayed nuclear condensation and aberrant elongation. As a result, mutant spermatids are characterized by the presence of residual cytoplasm, acrosome detachment, and fragmented DNA. Hence, H1T2 is a protein required for proper cell restructuring and DNA condensation during the elongation phase of spermiogenesis.