HP1 proteins compact DNA into mechanically and positionally stable phase separated domains.
HP1 proteins compact DNA into mechanically and positionally stable phase separated domains.
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DOI：
10.7554/elife.64563
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发表时间：
2021-03-04
期刊：
影响因子：
7.7
通讯作者：
Redding S
中科院分区：
文献类型：
--
作者：
Keenen MM;Brown D;Brennan LD;Renger R;Khoo H;Carlson CR;Huang B;Grill SW;Narlikar GJ;Redding S
在哺乳动物中，HP 1介导的异染色质形成位置和机械稳定的基因组结构域，即使组分HP 1旁系同源物HP 1 α、HP 1 β和HP 1 γ显示出快速的开-关动力学。在这里，我们调查是否相分离的HP 1蛋白可以解释这些生物学观察。使用本体和单分子方法，我们表明，在相分离的HP 1 α-DNA凝聚物，HP 1 α作为一个动态的液体，而紧凑的DNA分子被限制在本地领土。这些冷凝物能抵抗很大的力，但很容易被HP 1 β溶解。最后，我们发现每个HP 1粒子的DNA压缩和相分离特性的差异产生于它们各自的无序区域。我们的研究结果表明，一个普遍的模型，基因组组织中，一个池的弱结合蛋白质集体利用DNA的聚合物特性，产生自组织结构域，同时抵抗大的力量在中尺度和分子尺度上的竞争。
In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog’s DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.