Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development.

Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development.
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小鼠Chd 4-β D是新生精原细胞存活和正常性腺发育所必需的。

DOI:
10.1186/s13072-022-00448-5
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发表时间:
2022-05-14
影响因子:
3.9
通讯作者:
Pezza, Roberto J.
Pezza, Roberto J.
中科院分区:
生物学2区
文献类型:
--
作者:
de Castro, Rodrigo O.;Carbajal, Agustin;Previato de Almeida, Luciana;Goitea, Victor;Griffin, Courtney T.;Pezza, Roberto J.

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成年人睾丸的发育和生殖细胞的持续产生依赖于精原干细胞的建立和维持及其向精母细胞的适当分化。染色质重塑复合物通过限制或促进DNA修复和基因表达机制对染色质的可及性来调节配子发育期间的关键过程。在这里,我们调查的作用,Chd 4和Chd 3催化亚基的BHD复合物在精子发生过程中。生殖细胞特异性chd 4在配子发生早期的缺失,而不是chd 3,导致早期配子发育停滞,由于新生儿未分化精原干细胞群的细胞存活失败。候选人评估显示,Chd 4控制dmrt 1及其下游靶点plzf的表达,两者都被描述为精原干细胞维持的重要调节因子。我们的研究结果表明,在哺乳动物配子发生的要求Chd 4指向功能的基因表达的早期过程中。在线版本包含补充材料,可通过10.1186/s13072-022-00448-5获得。
Testis development and sustained germ cell production in adults rely on the establishment and maintenance of spermatogonia stem cells and their proper differentiation into spermatocytes. Chromatin remodeling complexes regulate critical processes during gamete development by restricting or promoting accessibility of DNA repair and gene expression machineries to the chromatin. Here, we investigated the role of Chd4 and Chd3 catalytic subunits of the NURD complex during spermatogenesis. Germ cell-specific deletion of chd4 early in gametogenesis, but not chd3, resulted in arrested early gamete development due to failed cell survival of neonate undifferentiated spermatogonia stem cell population. Candidate assessment revealed that Chd4 controls expression of dmrt1 and its downstream target plzf, both described as prominent regulators of spermatogonia stem cell maintenance. Our results show the requirement of Chd4 in mammalian gametogenesis pointing to functions in gene expression early in the process. The online version contains supplementary material available at 10.1186/s13072-022-00448-5.
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