深圳湾实验室张浩岳小组在研究中取得进展。他们报道了在凝聚蛋白耗尽的有丝分裂染色体中揭示基因组折叠原理。2024年5月27日出版的《自然—遗传学》发表了这项成果。

据介绍，在有丝分裂过程中，凝缩蛋白的活性被认为干扰了间期染色质结构。

为了研究在没有染色质环外移离子的情况下基因组折叠原理，课题组共缺失凝聚蛋白I和凝聚蛋白II，它们以类似于在间期的方式触发有丝分裂染色体区隔化。然而，在凝聚蛋白丢失时，出现了两个在间期无法区分的明显的常染色质部分，它们具有不同的相互作用偏好和对H3K27ac的依赖性。组成型异染色质逐渐自我聚集并与兼性异染色质共组份，与间期的分离形成对比。

值得注意的是，即使在没有CTCF/内聚蛋白介导结构的情况下，一些顺式调节元件的接触也变得明显。异染色质蛋白1 (HP1)被认为是分割组成性异染色质的蛋白，但在有丝分裂染色体中却不存在，这令人惊讶地表明，没有HP1，组成性异染色质也可以自我聚集。事实上，在细胞从M期到G1期，在HP1α、HP1β和HP1γ缺失的情况下，组成性异染色质室通常会重新建立。总之，凝聚蛋白缺乏的有丝分裂染色体阐明了，间期细胞中未发现的基因组区隔化的力量。

附：英文原文

Title: Genome folding principles uncovered in condensin-depleted mitotic chromosomes

Author: Zhao, Han, Lin, Yinzhi, Lin, En, Liu, Fuhai, Shu, Lirong, Jing, Dannan, Wang, Baiyue, Wang, Manzhu, Shan, Fengnian, Zhang, Lin, Lam, Jessica C., Midla, Susannah C., Giardine, Belinda M., Keller, Cheryl A., Hardison, Ross C., Blobel, Gerd A., Zhang, Haoyue

Issue&Volume: 2024-05-27

Abstract: During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1β and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.

DOI: 10.1038/s41588-024-01759-x

Source: https://www.nature.com/articles/s41588-024-01759-x