有丝分裂向 G1 转变过程中微室形成的动态变化

Viraat Y Goel, Nicholas G Aboreden, James M Jusuf, Haoyue Zhang, Luisa Mori, Leonid A Mirny, Gerd Blobel, Edward J Banigan, Anders Sejr Hansen
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引用次数: 0

摘要

当细胞退出有丝分裂进入 G1 期时,有丝分裂染色体会解聚,转录也会重新建立。之前的 Hi-C 研究表明,在有丝分裂过程中,基本上所有间期三维基因组特征都会消失,包括 A/B 小室、TAD 和 CTCF 环。然而,Hi-C 对微空腔、嵌套的顺式调控元件(CRE)之间的焦点相互作用等特征仍然不敏感。因此,我们对有丝分裂至 G1 期的细胞进行了区域捕获 Micro-C。出乎意料的是,我们在有丝分裂期观察到了微小空隙,这种空隙在有丝分裂期/分裂期进一步加强,然后在 G1 期逐渐减弱。冷凝素耗竭导致的环路挤压损失对微空腔和大 A/B 空腔产生了不同的影响,这表明它们有部分区别。通过聚合物建模,我们发现染色质压实有利于微隔室的形成,而环路挤压活动则不利于微隔室的形成,这就解释了为什么ana/telophase可能提供了一个特别有利的环境。我们的研究结果表明,CREs 表现出内在的同型亲和力,从而导致微室的形成,这或许可以解释有丝分裂结束时观察到的瞬时转录尖峰现象。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamics of microcompartment formation at the mitosis-to-G1 transition
As cells exit mitosis and enter G1, mitotic chromosomes decompact and transcription is reestablished. Previously, Hi-C studies showed that essentially all interphase 3D genome features including A/B-compartments, TADs, and CTCF loops, are lost during mitosis. However, Hi-C remains insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements (CREs). We therefore applied Region Capture Micro-C to cells from mitosis to G1. Unexpectedly, we observe microcompartments in prometaphase, which further strengthen in ana/telophase before gradually weakening in G1. Loss of loop extrusion through condensin depletion differentially impacts microcompartments and large A/B-compartments, suggesting that they are partially distinct. Using polymer modeling, we show that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion activity, explaining why ana/telophase likely provides a particularly favorable environment. Our results suggest that CREs exhibit intrinsic homotypic affinity leading to microcompartment formation, which may explain transient transcriptional spiking observed upon mitotic exit.
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