The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved
The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved
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DOI：
10.1007/s00412-004-0281-9
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发表时间：
2004-05-01
期刊：
影响因子：
1.6
通讯作者：
Allis, CD
中科院分区：
文献类型：
--
作者：
Barber, CM;Turner, FB;Allis, CD
长期以来，组蛋白磷酸化与有丝分裂染色质凝聚有关；然而，这些修饰的功能作用尚不清楚。在许多生物体中，组蛋白H1和H3从G2晚期到末期都被高度磷酸化，并与染色质凝聚和姐妹染色单体分离有关。然而，酵母的突变分析和爪蟾提取物的生化实验表明，H1和H3的磷酸化在这些过程中不是必需的。在这项研究中，我们研究了有丝分裂过程中可能对H1和H3磷酸化具有冗余功能的额外组蛋白磷酸化事件。我们开发了一种针对H4和H2A的抗体，它们各自的丝氨酸1 （S1）残基磷酸化，发现H4S1/H2AS1在蠕虫、苍蝇和哺乳动物的有丝分裂染色质中高度磷酸化。有丝分裂H4/H2A磷酸化与H3磷酸化具有相似的时间和定位，并与有丝分裂过程中染色质凝聚事件密切相关。我们还在5-溴-2-脱氧尿苷阳性的s期细胞中检测到较低水平的H4/H2A磷酸化，这证实了早期研究中在s期新合成的组蛋白上发现的H4S1磷酸化。H4/H2A在细胞周期中的进化保守磷酸化表明它们可能在有丝分裂期间的染色质凝聚和s期的组蛋白沉积中具有双重作用。
Histone phosphorylation has long been associated with condensed mitotic chromatin; however, the functional roles of these modifications are not yet understood. Histones H1 and H3 are highly phosphorylated from late G2 through telophase in many organisms, and have been implicated in chromatin condensation and sister chromatid segregation. However, mutational analyses in yeast and biochemical experiments with Xenopus extracts have demonstrated that phosphorylation of H1 and H3 is not essential for such processes. In this study, we investigated additional histone phosphorylation events that may have redundant functions to H1 and H3 phosphorylation during mitosis. We developed an antibody to H4 and H2A that are phosphorylated at their respective serine 1 (S1) residues and found that H4S1/H2AS1 are highly phosphorylated in the mitotic chromatin of worm, fly, and mammals. Mitotic H4/H2A phosphorylation has similar timing and localization as H3 phosphorylation, and closely correlates with the chromatin condensation events during mitosis. We also detected a lower level of H4/H2A phosphorylation in 5-bromo-2-deoxyuridine-positive S-phase cells, which corroborates earlier studies that identified H4S1 phosphorylation on newly synthesized histones during S-phase. The evolutionarily conserved phosphorylation of H4/H2A during the cell cycle suggests that they may have a dual purpose in chromatin condensation during mitosis and histone deposition during S-phase.