Human Male Meiotic Sex Chromosome Inactivation
Human Male Meiotic Sex Chromosome Inactivation
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DOI：
10.1371/journal.pone.0031485
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发表时间：
2012-02-15
期刊：
影响因子：
3.7
通讯作者：
de Boer, Peter
中科院分区：
文献类型：
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作者：
de Vries, Marieke;Vosters, Sanne;de Boer, Peter
在哺乳动物雄性配子发生中，性染色体在基因活性和表观遗传策略上都是独一无二的。在减数分裂前期，异形的X和Y染色体被放置在单独的染色质区域中，称为XY小体。在这个过程中，X，Y染色质在H_2AX的S139处高度磷酸化，导致淋体基因的抑制，这一过程被称为减数分裂性染色体失活(MSCI)，这一过程在小鼠中研究得最好。后中期，这种压制在很大程度上得到了维持。小鼠骨髓间充质干细胞功能紊乱会导致有害的X、Y基因表达，最终导致精母细胞死亡和精子异质性。精子的异质性是人类男性的一个特征。出于这个原因，我们对MSCI在人类初级精母细胞中的效率感兴趣。我们用直接和间接原位方法研究了7名先证者(4名不育男性和3名生育对照组)粗线期精母细胞中的MSCI。无论是在先证者之间还是在先证者内部，MSCI的程度都有相当大的差异。此外，在减数分裂后阶段也观察到这种变异，表明带有未完全失活的性染色体的精母细胞存活。此外，我们还研究了H3K9me3对X和Y染色质的翻译后修饰的存在。与构成着丝粒的异染色质相反，除了Y染色体的异染色质部分外，该异染色质标记并不特异性地聚集在XY小体上。这可能反映了与小鼠相比，人的MSCI程度较低。这些结果指向MSCI的松弛，这可以用进化过程中性染色体组成的遗传变化来解释，并可能是人类精子异质性背后的一个机制。
In mammalian male gametogenesis the sex chromosomes are distinctive in both gene activity and epigenetic strategy. At first meiotic prophase the heteromorphic X and Y chromosomes are placed in a separate chromatin domain called the XY body. In this process, X, Y chromatin becomes highly phosphorylated at S139 of H2AX leading to the repression of gonosomal genes, a process known as meiotic sex chromosome inactivation (MSCI), which has been studied best in mice. Post-meiotically this repression is largely maintained. Disturbance of MSCI in mice leads to harmful X, Y gene expression, eventuating in spermatocyte death and sperm heterogeneity. Sperm heterogeneity is a characteristic of the human male. For this reason we were interested in the efficiency of MSCI in human primary spermatocytes. We investigated MSCI in pachytene spermatocytes of seven probands: four infertile men and three fertile controls, using direct and indirect in situ methods. A considerable degree of variation in the degree of MSCI was detected, both between and within probands. Moreover, in post-meiotic stages this variation was observed as well, indicating survival of spermatocytes with incompletely inactivated sex chromosomes. Furthermore, we investigated the presence of H3K9me3 posttranslational modifications on the X and Y chromatin. Contrary to constitutive centromeric heterochromatin, this heterochromatin marker did not specifically accumulate on the XY body, with the exception of the heterochromatic part of the Y chromosome. This may reflect the lower degree of MSCI in man compared to mouse. These results point at relaxation of MSCI, which can be explained by genetic changes in sex chromosome composition during evolution and candidates as a mechanism behind human sperm heterogeneity.