Institute of Molecular Medicine, National Taiwan University, Taipei 100, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Department of Life Science, National Taiwan Ocean University, Keelung, Taiwan 20224; Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan 20224.
J Biol Chem. 2011 Oct 14;286(41):35843-35851. doi: 10.1074/jbc.M111.228064. Epub 2011 Aug 18.
Global histone H1 phosphorylation correlates with cell cycle progression. However, the function of site-specific H1 variant phosphorylation remains unclear. Our mass spectrometry analysis revealed a novel N-terminal phosphorylation of the major H1 variant H1.4 at serine 35 (H1.4S35ph), which accumulates at mitosis immediately after H3 phosphorylation at serine 10. Protein kinase A (PKA) was found to be a kinase for H1.4S35. Importantly, Ser-35-phosphorylated H1.4 dissociates from mitotic chromatin. Moreover, H1.4S35A substitution mutant cannot efficiently rescue the mitotic defect following H1.4 depletion, and inhibition of PKA activity increases the mitotic chromatin compaction depending on H1.4. Our results not only indicate that PKA-mediated H1.4S35 phosphorylation dissociates H1.4 from mitotic chromatin but also suggest that this phosphorylation is necessary for specific mitotic functions.
全球组蛋白 H1 磷酸化与细胞周期进程相关。然而，特定位置的 H1 变体磷酸化的功能仍不清楚。我们的质谱分析显示主要 H1 变体 H1.4 的 N 端丝氨酸 35 （H1.4S35ph）发生了新型磷酸化，该磷酸化在 H3 丝氨酸 10 磷酸化后立即在有丝分裂中积累。发现蛋白激酶 A（PKA）是 H1.4S35 的激酶。重要的是，磷酸化的 H1.4 从有丝分裂染色质上解离。此外，H1.4S35A 取代突变体不能有效挽救 H1.4 耗尽后有丝分裂缺陷，并且 PKA 活性的抑制会增加 H1.4 依赖性的有丝分裂染色质紧缩。我们的结果不仅表明 PKA 介导的 H1.4S35 磷酸化使 H1.4 从有丝分裂染色质上解离，还表明这种磷酸化对于特定的有丝分裂功能是必要的。
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