Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation

Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation
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DOI:
10.1007/s004120050256
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发表时间:
1997-11-01
期刊:
影响因子:
1.6
通讯作者:
Allis, CD
Allis, CD
中科院分区:
生物学3区
文献类型:
--
作者:
Hendzel, MJ;Wei, Y;Allis, CD

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我们已经生成并表征了一种新型位点特异性抗体,该抗体对组蛋白 H3 (Ser10) 氨基末端的磷酸化形式具有高度特异性。在本研究中,我们使用该抗体详细检查了哺乳动物细胞中 H3 磷酸化与有丝分裂染色体浓缩之间的关系。我们的结果扩展了之前的生化研究,证明H3的有丝分裂磷酸化在G2间期晚期细胞的着丝粒周围异染色质中非随机启动。起始后,H3 磷酸化似乎扩散到整个浓缩染色质,并且在大多数细胞系中在前期染色体形成之前完成,其中观察到磷酸化但非有丝分裂的染色体组织。一般来说,H3 磷酸化和染色质浓缩初始阶段之间存在精确的空间和时间相关性。 H3 的去磷酸化在后期开始,并在末期细胞中可检测到的染色体去浓缩之前完成。我们认为组蛋白 H3 氨基末端的单一磷酸化可能参与促进有丝分裂期间的两个关键功能:(1)调节蛋白质相互作用以促进反式作用因子的结合,这些因子在细胞进入 M 期时“驱动”染色质浓缩;(2)协调与 M 期相关的染色质解浓缩。
We have generated and characterized a novel site-specific antibody highly specific for the phosphorylated form of the amino-terminus of histone H3 (Ser10). In this study, we used this antibody to examine in detail the relationship between H3 phosphorylation and mitotic chromosome condensation in mammalian cells. Our results extend previous biochemical studies by demonstrating that mitotic phosphorylation of H3 initiates nonrandomly in pericentromeric heterochromatin in late G2 interphase cells. Following initiation, H3 phosphorylation appears to spread throughout the condensing chromatin and is complete in most cell lines just prior to the formation of prophase chromosomes, in which a phosphorylated, but nonmitotic, chromosomal organization is observed. In general, there is a precise spatial and temporal correlation between H3 phosphorylation and initial stages of chromatin condensation. Dephosphorylation of H3 begins in anaphase and is complete immediately prior to detectable chromosome decondensation in telophase cells. We propose that the singular phosphorylation of the amino-terminus of histone H3 may be involved in facilitating two key functions during mitosis: (1) regulate protein protein interactions to promote binding of trans-acting factors that ''drive'' chromatin condensation as cells enter M-phase and (2) coordinate chromatin decondensation associated with M-phase.