A quantitative map of human Condensins provides new insights into mitotic chromosome architecture
A quantitative map of human Condensins provides new insights into mitotic chromosome architecture
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DOI：
10.1083/jcb.201801048
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发表时间：
2018-07-01
影响因子：
7.8
通讯作者：
Ellenberg, Jan
中科院分区：
文献类型：
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作者：
Walther, Nike;Hossain, M. Julius;Ellenberg, Jan
人类细胞中的这两种凝集素复合体是有丝分裂染色体结构所必需的。我们使用纯合子基因组编辑来荧光标记凝聚素I和II亚基，并通过荧光相关光谱(FSC)校准的活细胞成像和超分辨率显微镜绘制了它们的绝对丰度、间距和有丝分裂期间的动态定位。虽然类似于35,000个凝聚素II复合体在整个有丝分裂过程中稳定地与染色体结合，但类似于195,000个凝聚素I复合体在有丝分裂过程中动态结合分为两个步骤：前期和后期。这两种凝聚素很少在染色单体轴上共定位，凝聚素II集中在染色单体轴上，但凝聚素I从其中心达到染色单体直径的50%。基于我们的全面的定量数据，我们提出了一个有丝分裂染色体压缩的三步层次环模型：凝聚素II最初在染色单体轴上固定最大尺寸类似于450kb的环，然后通过凝聚素I结合缩小其大小，使其在中期接近90kb，在后期接近70kb，从而在姐妹染色单体分离时实现最大的染色体压缩。
The two Condensin complexes in human cells are essential for mitotic chromosome structure. We used homozygous genome editing to fluorescently tag Condensin I and II subunits and mapped their absolute abundance, spacing, and dynamic localization during mitosis by fluorescence correlation spectroscopy (FSC)-calibrated live-cell imaging and superresolution microscopy. Although similar to 35,000 Condensin II complexes are stably bound to chromosomes throughout mitosis, similar to 195,000 Condensin I complexes dynamically bind in two steps: prometaphase and early anaphase. The two Condensins rarely colocalize at the chromatid axis, where Condensin II is centrally confined, but Condensin I reaches similar to 50% of the chromatid diameter from its center. Based on our comprehensive quantitative data, we propose a three-step hierarchical loop model of mitotic chromosome compaction: Condensin II initially fixes loops of a maximum size of similar to 450 kb at the chromatid axis, whose size is then reduced by Condensin I binding to similar to 90 kb in prometaphase and similar to 70 kb in anaphase, achieving maximum chromosome compaction upon sister chromatid segregation.