Spermatogenesis-specific association of SMCY and MSH5
Spermatogenesis-specific association of SMCY and MSH5
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DOI：
10.1111/j.1365-2443.2008.01193.x
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发表时间：
2008-06-01
期刊：
影响因子：
2.1
通讯作者：
Kato, Shigeaki
中科院分区：
文献类型：
--
作者：
Akimoto, Chihiro;Kitagawa, Hirochika;Kato, Shigeaki
精子发生过程中染色质的状态受特定组蛋白编码或阶段特异性组蛋白变化的动态调节。这种表观遗传调控和调节减数分裂的蛋白质之间的功能联系在很大程度上是未知的。在哺乳动物中，Y染色体上编码的基因被认为具有男性特异性的生物学功能。虽然位于无精子因子区域（AZF）内的基因已知参与精子发生，但单个基因的生理功能尚不清楚。SMCY是定位于AZF的一个基因，在本报告中，我们分析了SMCY蛋白在精子发生过程中的功能。与之相互作用的蛋白质的生化鉴定表明，SMCY与MSH5形成了一种独特的复合物，MSH5是人类睾丸生殖细胞系NEC 8中的一种关键减数分裂调节蛋白。正如预期的那样，检测到组蛋白H3K4脱甲基酶活性。免疫组化分析显示SMCY与MSH5在小鼠精子发生过程中减数分裂前期进展的特定阶段共定位。我们的研究结果表明，SMCY可能有一个男性特异性的功能，作为组蛋白H3K4去甲基化酶通过招募减数分裂调节蛋白凝聚的DNA。
The status of chromatin during spermatogenesis is dynamically regulated by specific histone codes or stage-specific histone changes. The functional links between such epigenetic regulation and proteins regulating meiosis are largely unknown. In mammals, genes encoded on the Y chromosome are thought to possess male-specific biological functions. While genes located within the azoospermia factor region (AZF) are known to be involved in spermatogenesis, the physiological function of individual genes is not known. SMCY is a gene mapped to the AZF, and in this report, we analyzed the function of SMCY protein during spermatogenesis. Biochemical identification of the proteins with which it interacted showed that SMCY formed a distinct complex with MSH5, a critical meiosis-regulatory protein in the human testicular germ cell line, NEC8. As anticipated, histone H3K4 demethylase activity was detected. Immunohistochemical analysis revealed the co-localization of SMCY with MSH5 at a specific stage of meiotic prophase progression during murine spermatogenesis. Our results suggest that SMCY may have a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein to condensed DNA.