Meiotic events at the centromeric heterochromatin:: histone H3 phosphorylation, topoisomerase IIα localization and chromosome condensation
Meiotic events at the centromeric heterochromatin:: histone H3 phosphorylation, topoisomerase IIα localization and chromosome condensation
复制标题
DOI：
10.1007/s004120050393
复制
发表时间：
1999-12-01
期刊：
影响因子：
1.6
通讯作者：
Handel, MA
中科院分区：
文献类型：
--
作者：
Cobb, J;Miyaike, M;Handel, MA
第一次减数分裂中染色体凝聚和分离的机制还不是很清楚。分解重组事件以形成交叉是重要的，因为是交叉将同源染色体聚集在一起，因为它们在减数分裂中期纺锤体上的相反方向，从而确保它们在后期I的准确分离。着丝粒上的事件对于实现与纺锤体的正确连接也是重要的。本研究旨在探讨小鼠精母细胞着丝粒异染色质中拓扑异构酶IIα(TOP2A)和组蛋白H3两种蛋白质的存在和活性与染色体凝聚和交叉配子体二价体个体化的关系。我们验证了组蛋白H3的磷酸化是一个关键事件，该事件促使TOP2A定位到着丝粒异染色质，并在精母细胞退出前期并进展到中期时染色体凝聚。在减数分裂前期结束时，染色质的缩合需要拓扑异构酶II的活性。组蛋白H3在前期末期发生磷酸化，在双线期的着丝粒异染色质开始磷酸化。然而，它不能参与TOP2A的定位，因为TOP2A在减数分裂前期的大部分时间都定位于着丝粒异染色质。这一观察结果表明，TOP2A除了在染色质缩合中发挥作用外，还具有减数分裂功能。激酶抑制剂的使用表明，组蛋白H3的ChAT磷酸化可以从减数分裂染色体凝聚中解偶联，因此必须涉及其他蛋白质，如那些构成中期促进因子的蛋白质。这些结果定义了着丝粒异染色质重要减数分裂事件的时间，并为了解减数分裂中期染色体凝聚的机制提供了洞察力。
Mechanisms of chromosome condensation and segregation during the first meiotic division are not well understood. Resolution of recombination events to form chiasmata is important, for it is chiasmata that hold homologous chromosomes together for their oppositional orientation on the meiotic metaphase spindle, thus ensuring their accurate segregation during anaphase I. Events at the centromere are also important in bringing about proper attachment to the spindle apparatus. This study was designed to correlate the presence and activity of two proteins at the centromeric heterochromatin, topoisomerase II alpha (TOP2A) and histone H3, with the processes of chromosome condensation and individualization of chiasmate bivalents in murine spermatocytes. We tested the hypothesis that phosphorylation of histone H3 is a key event instigating localization of TOP2A to the centromeric heterochromatin and condensation of chromosomes as spermatocytes exit prophase and progress to metaphase. Activity of topoisomerase II is required for condensation of chromatin at the end of meiotic prophase. Histone H3 becomes phosphorylated at the end of prophase, beginning with its phosphorylation at the centromeric heterochromatin in the diplotene stage. However, it cannot be involved in localization of TOP2A, since TOP2A is localized to the centromeric heterochromatin throughout most of meiotic prophase. This observation suggests a meiotic function for TOP2A in addition to its role in chromatin condensation. The use of kinase inhibitors demonstrates chat phosphorylation of histone H3 can be uncoupled from meiotic chromosome condensation; therefore other proteins, such as those constituting metaphase-promoting factor, must be involved. These results define the timing of important meiotic events at the centromeric heterochromatin and provide insight into mechanisms of chromosome condensation for meiotic metaphase.