Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation
Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation
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DOI：
10.7554/elife.10396
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发表时间：
2015-11-28
期刊：
影响因子：
7.7
通讯作者：
Barral, Yves
中科院分区：
文献类型：
--
作者：
Kruitwagen, Tom;Denoth-Lippuner, Annina;Barral, Yves
真核细胞染色体在有丝分裂过程中的分离需要它们广泛地折叠成适合有丝分裂纺锤体的大小单位。在这里，我们报告了组蛋白H3(H3S10)的丝氨酸10处的磷酸化是如何促进这一过程的。使用基于荧光的方法来研究活的酵母细胞中染色质纤维的局部紧致，我们发现染色体凝聚需要两个在时间和机械上不同的过程。最初，组蛋白H4的H3S10磷酸化和去乙酰化引发的核小体-核小体相互作用促进了染色质在早期后期的短期紧致。凝聚素独立地调节染色体臂的轴向收缩，这一过程在后期达到顶峰。尽管染色质压缩的缺陷对轴向收缩没有明显的影响，凝集素失活也不会影响染色质的短程压缩，但这两条途径的失活都会导致染色体分离和细胞活力的协同缺陷。此外，这两条途径至少部分依赖于脱乙酰酶HST2，这表明该蛋白有助于协调染色质压缩和轴向收缩，以适当地塑造有丝分裂染色体。
The segregation of eukaryotic chromosomes during mitosis requires their extensive folding into units of manageable size for the mitotic spindle. Here, we report on how phosphorylation at serine 10 of histone H3 (H3S10) contributes to this process. Using a fluorescence-based assay to study local compaction of the chromatin fiber in living yeast cells, we show that chromosome condensation entails two temporally and mechanistically distinct processes. Initially, nucleosome-nucleosome interaction triggered by H3 S10 phosphorylation and deacetylation of histone H4 promote short-range compaction of chromatin during early anaphase. Independently, condensin mediates the axial contraction of chromosome arms, a process peaking later in anaphase. Whereas defects in chromatin compaction have no observable effect on axial contraction and condensin inactivation does not affect short-range chromatin compaction, inactivation of both pathways causes synergistic defects in chromosome segregation and cell viability. Furthermore, both pathways rely at least partially on the deacetylase Hst2, suggesting that this protein helps coordinating chromatin compaction and axial contraction to properly shape mitotic chromosomes.