Histone ubiquitination and chromatin remodeling in mouse spermatogenesis
Histone ubiquitination and chromatin remodeling in mouse spermatogenesis
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DOI：
10.1006/dbio.1998.9155
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发表时间：
1999-03-15
影响因子：
2.7
通讯作者：
Grootegoed, JA
中科院分区：
文献类型：
--
作者：
Baarends, WM;Hoogerbrugge, TW;Grootegoed, JA
HR6B 敲除小鼠的雄性不育与精子发生受损有关。 HR6B 基因是哺乳动物、酿酒酵母基因 Rad6 的常染色体同源物，编码泛素结合酶。此外，已在人类和小鼠体内鉴定出 X 染色体 HR6A。酵母中的 RAD6 是多种细胞功能所必需的，包括孢子形成、DNA 修复和诱变。由于 RAD6 及其哺乳动物同源物可以在体外泛素化组蛋白，因此我们研究了小鼠睾丸中组蛋白泛素化的模式。通过对野生型小鼠睾丸进行免疫印迹和免疫组织化学分析，在粗线期精母细胞中检测到大量泛素化 H2A (uH2A)。这种信号在圆形精子细胞中变得不可检测到，但在相对较短的发育时期，在伸长的精子细胞中再次增加。没有观察到其他泛素化组蛋白。在 HR6B 敲除小鼠中，我们未能检测到组蛋白泛素化整体模式的明显缺陷。对于体细胞类型，已表明组蛋白泛素化与核小体的不稳定有关，与活性基因有关；转录。出乎意料的是，粗线期精母细胞中最强烈的uH2A信号在性体中检测到，性体是一种包含异染色质X和Y染色体的不活跃核结构。伸长精细胞中减数分裂后 uH2A 免疫表达表明，组蛋白泛素化诱导的核小体不稳定可能在组蛋白到鱼精蛋白的替代过程中发挥促进作用。 (C) 1999 年学术出版社。
Male infertility in HR6B knockout mice is associated with impairment of spermatogenesis. The HR6B gene is a mammalian, autosomal homolog of the Saccharomyces cerevisiae gene Rad6 encoding a ubiquitin-conjugating enzyme. In addition, X-chromosomal HR6A has been identified, in human and mouse. RAD6 in yeast is required for a variety of cellular functions, including sporulation, DNA repair, and mutagenesis. Since RAD6 and its mammalian homologs can ubiquitinate histones in vitro, we have investigated the pattern of histone ubiquitination in mouse testis. By immunoblot and immunohistochemical analysis of wild-type mouse testis, a high amount of ubiquitinated H2A (uH2A) was detected in pachytene spermatocytes. This signal became undetectable in round spermatids, but then increased again during a relatively short developmental period, in elongating spermatids. No other ubiquitinated histones were observed. In the HR6B knockout mice, we failed to detect an overt defect in the overall pattern of histone ubiquitination. For somatic cell types, it has been shown that histone ubiquitination is associated with destabilization of nucleosomes, in relation to active gene; transcription. Unexpectedly, the most intense uH2A signal in pachytene spermatocytes was detected in the sex body, an inactive nuclear structure that contains the heterochromatic X and Y chromosomes. The postmeiotic uH2A immunoexpression in elongating spermatids indicates that nucleosome destabilization induced by histone ubiquitination may play a facilitating role during histone-to-protamine replacement. (C) 1999 Academic Press.