A histone code in meiosis:: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes
A histone code in meiosis:: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes
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DOI：
10.1101/gad.1348905
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发表时间：
2005-11-01
影响因子：
10.5
通讯作者：
Orr-Weaver, TL
中科院分区：
文献类型：
--
作者：
Ivanovska, I;Khandan, T;Orr-Weaver, TL
在有性生殖过程中，为了促进遗传物质的忠实繁殖，减数分裂染色体经历了特殊的形态变化，以确保同源染色体的准确分离。建立减数分裂染色体结构的分子机制在很大程度上是未知的。我们描述了最近在果蝇中发现的组蛋白H2A激酶（nhk-1）的突变，该突变由于减数分裂染色体结构形成缺陷而导致雌性不育。中期I阻滞和核小体，一个关键的前期I染色体结构，需要核小体组蛋白激酶-1 （NHK-1）的功能。这些缺陷是由于无法分解突触复合体和将凝聚蛋白装载到突变染色体上。由nhk-1（-/-）突变雌性产下的胚胎在极体和有丝分裂纺锤体异常的情况下停滞，表明有丝分裂也受到影响。我们根据组蛋白编码假说分析了Histone H2A磷酸化的作用，发现它是减数分裂中Histone H3和Histone H4乙酰化所必需的。这些研究揭示了组蛋白修饰在减数分裂和有丝分裂中染色体动力学中的关键作用。
To promote faithful propagation of the genetic material during sexual reproduction, meiotic chromosomes undergo specialized morphological changes that ensure accurate segregation of homologous chromosomes. The molecular mechanisms that establish the meiotic chromosomal structures are largely unknown. We describe a mutation in a recently identified Histone H2A kinase, nhk-1, in Drosophila that leads to female sterility due to defects in the formation of the meiotic chromosomal structures. The metaphase I arrest and the karyosome, a critical prophase I chromosomal structure, require nucleosomal histone kinase-1 (NHK-1) function. The defects are a result of failure to disassemble the synaptonemal complex and to load condensin onto the mutant chromosomes. Embryos laid by nhk-1(-/-) mutant females arrest with aberrant polar bodies and mitotic spindles, revealing that mitosis is affected as well. We analyzed the role of Histone H2A phosphorylation with respect to the histone code hypothesis and found that it is required for acetylation of Histone H3 and Histone H4 in meiosis. These studies reveal a critical role for histone modifications in chromosome dynamics in meiosis and mitosis.