研究揭示有絲分裂染色質結構動力學
作者：
小柯機器人發布時間：2019/11/28 14:04:24
美國費城兒童醫院Gerd A. Blobel和賓夕法尼亞大學Jennifer E. Phillips-Cremins研究組合作，發現從有絲分裂到G1相變過程中的染色質結構動力學。這一研究成果2019年11月27日在線發表在國際學術期刊《自然》上。
他們利用Hi-C技術檢測了高度純化的同步小鼠紅系細胞群體有絲分裂後染色體重組動力學，觀察到A / B隔室快速建立，然後逐漸增強和擴展。接觸結構域由「自下而上」形成-最初形成較小的亞TAD，然後融合為多結構域TAD結構。 CTCF部分保留在有絲分裂染色體上，並在後期或者末期立即恢復完全結合。相比之下，粘著素完全從有絲分裂染色體上清除，並以較慢的速度重新獲得焦點結合。CTCF /粘著蛋白共錨結構環的形成遵循粘著素定位動力學。由CTCF固定的條紋狀接觸模式的長度會增加，這與有絲分裂後的環擠壓過程一致。順式調節元件之間的相互作用可以迅速形成，其速率超過CTCF /粘著素錨定的接觸速率。值得注意的是，他們確定了在後期/末期的順式調控元件之間快速出現的一組瞬態接觸，這些接觸在進入G1時溶解，與內部邊界或附近的幹擾染色質環的建立同時發生。他們還描述了轉錄激活與體系結構特徵之間的關係。他們的研究結果表明，獨特但相互影響的力量推動了有絲分裂後染色質的重塑。
據介紹，高階染色質組織的特徵（例如A / B隔室、拓撲關聯域和染色質環）在有絲分裂過程中被暫時打亂。因為這些結構被認為會影響基因調控，所以了解它們在有絲分裂後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