A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis
A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis
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DOI：
10.1126/science.1244508
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发表时间：
2014-01-03
期刊：
影响因子：
56.9
通讯作者：
Neumann, Heinz
中科院分区：
文献类型：
--
作者：
Wilkins, Bryan J.;Rall, Nils A.;Neumann, Heinz
中期染色体是有丝分裂的明显标志，但我们对它们的结构和塑造它们的力量的理解还很初级。 Aurora B 激酶对组蛋白 H3 丝氨酸 10 (H3 S10) 的磷酸化是有丝分裂的标志性事件，但其在染色质浓缩中的功能尚不清楚。使用基因编码的紫外线诱导交联剂，我们在活酵母中以时空分辨率监测蛋白质-蛋白质相互作用，以确定 H3 S10 磷酸化下游途径的分子细节。这种修饰导致组蛋白脱乙酰酶 Hst2p 的募集，随后从组蛋白 H4 赖氨酸 16 上去除乙酰基，释放 H4 尾部以与邻近核小体表面相互作用并促进纤维缩合。这一级联事件提供了有丝分裂过程中染色质超浓缩的独立于凝缩蛋白的驱动力。
Metaphase chromosomes are visible hallmarks of mitosis, yet our understanding of their structure and of the forces shaping them is rudimentary. Phosphorylation of histone H3 serine 10 (H3 S10) by Aurora B kinase is a signature event of mitosis, but its function in chromatin condensation is unclear. Using genetically encoded ultraviolet light-inducible cross-linkers, we monitored protein-protein interactions with spatiotemporal resolution in living yeast to identify the molecular details of the pathway downstream of H3 S10 phosphorylation. This modification leads to the recruitment of the histone deacetylase Hst2p that subsequently removes an acetyl group from histone H4 lysine 16, freeing the H4 tail to interact with the surface of neighboring nucleosomes and promoting fiber condensation. This cascade of events provides a condensin-independent driving force of chromatin hypercondensation during mitosis.