JMJD1C Exhibits Multiple Functions in Epigenetic Regulation during Spermatogenesis.

JMJD1C Exhibits Multiple Functions in Epigenetic Regulation during Spermatogenesis.
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DOI:
10.1371/journal.pone.0163466
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Noce T
Noce T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nakajima R;Okano H;Noce T

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Jmjd 1C是Jmjd 1家族基因之一,编码针对组蛋白H3 K9和非组蛋白的脱甲基酶,已被证明在小鼠精子发生中发挥不可或缺的作用。在这里,我们分析了一个新培育的转基因小鼠品系携带Jmjd 1C功能丧失等位基因,其中β-geo盒整合到Jmjd 1C基因座的内含子。Jmjd 1C基因陷阱纯合子睾丸表现出减数分裂后的过程中的畸形和未分化的精原细胞的长期维持的缺陷。纯合子睾丸中的一些精子细胞群从精子发生的第一波开始就表现出异常的组织结构和不完全的伸长。此外,组蛋白H4 K16乙酰化,这是所需的染色质重塑的发病,似乎显着减少。这些效应可能不是与事件相关的基因表达急剧减少的结果,而是可能是由于JMJD 1C与其伴侣蛋白(如MDC 1和HSP 90)之间缺乏相互作用。此外,在Jmjd 1C纯合子成熟睾丸中发现Oct 4表达和表达NANOG和OCT 4的精原细胞显著减少,表明Jmjd 1C可能通过上调Oct 4表达参与维持精原干细胞自我更新。这些结果表明,JMJD 1C在精子发生过程中具有多种功能,通过与不同的伴侣在精子发生阶段的相互作用。
Jmjd1C is one of the Jmjd1 family genes that encode putative demethylases against histone H3K9 and non-histone proteins and has been proven to play an indispensable role in mouse spermatogenesis. Here, we analyzed a newly-bred transgenic mouse strain carrying a Jmjd1C loss-of-function allele in which a β-geo cassette was integrated into the intron of the Jmjd1C locus. Jmjd1C gene-trap homozygous testes exhibited malformations in postmeiotic processes and a deficiency in the long-term maintenance of undifferentiated spermatogonia. Some groups of spermatids in the homozygous testis showed abnormal organization and incomplete elongation from the first wave of spermatogenesis onwards. Moreover, histone H4K16 acetylation, which is required for the onset of chromatin remodeling, appeared to be remarkably decreased. These effects may not have been a result of the drastic decrease in gene expression related to the events but instead may have been due to the lack of interaction between JMJD1C and its partner proteins, such as MDC1 and HSP90. Additionally, significant decreases in Oct4 expression and NANOG- and OCT4-expressing spermatogonia were found in the Jmjd1C homozygous mature testis, suggesting that JMJD1C may participate in the maintenance of spermatogonial stem cell self-renewal by up-regulating Oct4 expression. These results indicate that JMJD1C has multiple functions during spermatogenesis through interactions with different partners during the spermatogenic stages.
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