Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis
Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis
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DOI：
10.1073/pnas.0406325101
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发表时间：
2004-11-23
影响因子：
11.1
通讯作者：
Driscoll, DJ
中科院分区：
文献类型：
--
作者：
Khalil, AM;Boyar, FZ;Driscoll, DJ
基于粗线期XY小体的形成和一些X连锁基因的表达研究，在哺乳动物精子发生过程中，X和Y染色体似乎经历了转录失活。然而，X和Y失活的程度和机制尚不清楚。在这里，我们表明，X和Y染色体进行连续的变化，在他们的组蛋白修饰开始在粗线期阶段的减数分裂。这些变化通常与体细胞中的转录失活有关，并且它们与从XY体中排除磷酸化（活性）形式的RNA聚合酶II一致。两条性染色体在组蛋白H3和H4处发生广泛的脱乙酰化，以及组蛋白H3上赖氨酸（K）9的（去）甲基化;然而，H3-K4甲基化没有变化。即使XY染色体在粗线期晚期消失，并且X和Y染色体在第一次减数分裂后彼此分离，这些变化仍然存在。到精子阶段，X和Y染色体的组蛋白修饰恢复到活性染色质的组蛋白修饰，RNA聚合酶II与两条染色体重新接合。我们的观察表明，X和Y失活是广泛的，并持续存在，即使当X和Y染色体在次级精母细胞分离。这些发现为男性生殖系的表观遗传编程和染色质动力学提供了见解。
Based on the formation of the XY body at pachytene and expression studies of a few X-linked genes, the X and Y chromosomes seem to undergo transcriptional inactivation during mammalian spermatogenesis. However, the extent and the mechanism of X and Y inactivation are not known. Here, we show that both the X and Y chromosomes undergo sequential changes in their histone modifications beginning at the pachytene stage of meiosis. These changes usually are associated with transcriptional inactivation in somatic cells, and they coincide with the exclusion of the phosphorylated (active) form of RNA polymerase II from the XY body. Both sex chromosomes undergo extensive deacetylation at histones H3 and H4 and (di)methylation of lysine (K)9 on histone H3; however, there are no changes in H3-K4 methylation. These changes persist even when the XY body disappears in late pachytene, and the X and Y chromosomes segregate from one another after the first meiotic division. By the spermatic stage, histone modifications of the X and Y chromosomes revert to those of active chromatin and RNA polymerase II reengages with both chromosomes. Our observations indicate that X and Y inactivation is extensive and persists even when the X and Y chromosomes are separated in secondary spermatocytes. These findings provide insights into epigenetic programming and chromatin dynamics in the male germ line.