Lancaster Oscar M, Cullen C Fiona, Ohkura Hiroyuki
The Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK.
J Cell Biol. 2007 Dec 3;179(5):817-24. doi: 10.1083/jcb.200706067. Epub 2007 Nov 26.
Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we report that phosphorylation of barrier to autointegration factor (BAF) by the conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a critical function in karyosome formation. We find that the noncatalytic domain of NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a linker between chromatin and the nuclear envelope. A reduction of NHK-1 or expression of nonphosphorylatable BAF results in ectopic association of chromosomes with the nuclear envelope in oocytes. We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms.
减数分裂中精确的染色体分离需要染色质组织的动态变化。在黑腹果蝇中，重组完成后，减数分裂染色体在增大的卵母细胞核中形成一个单一的、紧密的簇，称为染色质核仁。这种聚集在人类中也有发现；然而，染色质核仁形成的潜在机制尚不清楚。在这项研究中，我们报告保守激酶核小体组蛋白激酶-1（NHK-1；果蝇Vrk1）对自身整合因子（BAF）的磷酸化在染色质核仁形成中具有关键作用。我们发现NHK-1的非催化结构域对其针对BAF的激酶活性至关重要，BAF是一种在染色质和核膜之间起连接作用的蛋白质。NHK-1的减少或不可磷酸化的BAF的表达会导致卵母细胞中染色体与核膜的异位结合。我们提出，NHK-1对BAF的磷酸化破坏了染色体与核膜的锚定，从而允许卵母细胞中染色质核仁的形成。这些数据首次提供了关于染色质核仁如何形成的机制性见解。
