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研究揭示有丝分裂染色质结构动力学
作者:小柯机器人 发布时间:2019/11/28 14:04:24

美国费城儿童医院Gerd A. Blobel和宾夕法尼亚大学Jennifer E. Phillips-Cremins研究组合作,发现从有丝分裂到G1相变过程中的染色质结构动力学。这一研究成果2019年11月27日在线发表在国际学术期刊《自然》上。
 
他们利用Hi-C技术检测了高度纯化的同步小鼠红系细胞群体有丝分裂后染色体重组动力学,观察到A / B隔室快速建立,然后逐渐增强和扩展。接触结构域由“自下而上”形成-最初形成较小的亚TAD,然后融合为多结构域TAD结构。 CTCF部分保留在有丝分裂染色体上,并在后期或者末期立即恢复完全结合。相比之下,粘着素完全从有丝分裂染色体上清除,并以较慢的速度重新获得焦点结合。CTCF /粘着蛋白共锚结构环的形成遵循粘着素定位动力学。由CTCF固定的条纹状接触模式的长度会增加,这与有丝分裂后的环挤压过程一致。顺式调节元件之间的相互作用可以迅速形成,其速率超过CTCF /粘着素锚定的接触速率。值得注意的是,他们确定了在后期/末期的顺式调控元件之间快速出现的一组瞬态接触,这些接触在进入G1时溶解,与内部边界或附近的干扰染色质环的建立同时发生。他们还描述了转录激活与体系结构特征之间的关系。他们的研究结果表明,独特但相互影响的力量推动了有丝分裂后染色质的重塑。
 
据介绍,高阶染色质组织的特征(例如A / B隔室、拓扑关联域和染色质环)在有丝分裂过程中被暂时打乱。因为这些结构被认为会影响基因调控,所以了解它们在有丝分裂后如何重新建立非常重要。
 
附:英文原文

Title: Chromatin structure dynamics during the mitosis-to-G1 phase transition

Author: Haoyue Zhang, Daniel J. Emerson, Thomas G. Gilgenast, Katelyn R. Titus, Yemin Lan, Peng Huang, Di Zhang, Hongxin Wang, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Jennifer E. Phillips-Cremins, Gerd A. Blobel

Issue&Volume: 2019-11-27

Abstract: Features of higher-order chromatin organizationsuch as A/B compartments, topologically associating domains and chromatin loopsare temporarily disrupted during mitosis1,2. Because these structures are thought to influence gene regulation, it is important to understand how they are re-established after mitosis. Here we examine the dynamics of chromosome reorganization by Hi-C after mitosis in highly purified, synchronous mouse erythroid cell populations. We observed rapid establishment of A/B compartments, followed by their gradual intensification and expansion. Contact domains form from the bottom upsmaller subTADs are formed initially, followed by convergence into multi-domain TAD structures. CTCF is partially retained on mitotic chromosomes and immediately resumes full binding in ana/telophase. By contrast, cohesin is completely evicted from mitotic chromosomes and regains focal binding at a slower rate. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contact patternsanchored by CTCFgrow in length, which is consistent with a loop-extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly, with rates exceeding those of CTCF/cohesin-anchored contacts. Notably, we identified a group of rapidly emerging transient contacts between cis-regulatory elements in ana/telophase that are dissolved upon G1 entry, co-incident with the establishment of inner boundaries or nearby interfering chromatin loops. We also describe the relationship between transcription reactivation and architectural features. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin reconfiguration. Analysis of the dynamics of chromosome reorganization after exit from mitosis reveals the distinct but mutually influential forces that drive chromatin reconfiguration.

DOI: 10.1038/s41586-019-1778-y

Source:https://www.nature.com/articles/s41586-019-1778-y

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html