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RNA 聚合酶回溯导致裂殖酵母凝聚素在活性基因处积累。

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes.

机构信息

Laboratoire de Biologie et Modélisation de la Cellule, Université de Lyon, École Normale Supérieure de Lyon, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5239, Lyon, France.

Laboratoire de Biologie et Modélisation de la Cellule, Université de Lyon, École Normale Supérieure de Lyon, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5239, Lyon, France

出版信息

Life Sci Alliance. 2021 Mar 26;4(6). doi: 10.26508/lsa.202101046. Print 2021 Jun.

DOI:10.26508/lsa.202101046
PMID:33771877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8046420/
Abstract

The mechanisms leading to the accumulation of the SMC complexes condensins around specific transcription units remain unclear. Observations made in bacteria suggested that RNA polymerases (RNAPs) constitute an obstacle to SMC translocation, particularly when RNAP and SMC travel in opposite directions. Here we show in fission yeast that gene termini harbour intrinsic condensin-accumulating features whatever the orientation of transcription, which we attribute to the frequent backtracking of RNAP at gene ends. Consistent with this, to relocate backtracked RNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation of condensin at gene ends and to redistribute it evenly within transcription units, indicating that RNAP backtracking may play a key role in positioning condensin. Formalization of this hypothesis in a mathematical model suggests that the inclusion of a sub-population of RNAP with longer dwell-times is essential to fully recapitulate the distribution profiles of condensin around active genes. Taken together, our data strengthen the idea that dense arrays of proteins tightly bound to DNA alter the distribution of condensin on chromosomes.

摘要

导致 SMC 复合物凝聚素在特定转录单位周围积累的机制尚不清楚。在细菌中的观察结果表明，RNA 聚合酶（RNAP）构成了 SMC 易位的障碍，特别是当 RNAP 和 SMC 朝相反方向移动时。在这里，我们在裂殖酵母中表明，无论转录的方向如何，基因末端都具有内在的凝聚素积累特征，我们将其归因于 RNAP 在基因末端频繁的回溯。与此一致的是，将回溯的 RNAP2 从基因末端重新定位到基因体足以取消基因末端凝聚素的积累，并在转录单位内均匀地重新分配它，表明 RNAP 回溯可能在凝聚素定位中发挥关键作用。在数学模型中对该假设的形式化表明，包含具有更长停留时间的 RNAP 的亚群对于充分再现凝聚素在活性基因周围的分布特征是必不可少的。总之，我们的数据加强了这样一种观点，即紧密结合 DNA 的蛋白质密集阵列改变了染色体上凝聚素的分布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/e300b22577e2/LSA-2021-01046_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/4c4e382b96e2/LSA-2021-01046_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/d2441bee76ce/LSA-2021-01046_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/162a8234f8c6/LSA-2021-01046_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/e0ee5f9ce576/LSA-2021-01046_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/d5cb83855276/LSA-2021-01046_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/6e37cae27db7/LSA-2021-01046_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/359d0cbce935/LSA-2021-01046_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/e300b22577e2/LSA-2021-01046_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/4c4e382b96e2/LSA-2021-01046_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/d2441bee76ce/LSA-2021-01046_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/162a8234f8c6/LSA-2021-01046_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/e0ee5f9ce576/LSA-2021-01046_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/d5cb83855276/LSA-2021-01046_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/6e37cae27db7/LSA-2021-01046_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/359d0cbce935/LSA-2021-01046_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f49/8046420/e300b22577e2/LSA-2021-01046_FigS4.jpg

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Sci Adv. 2021 Feb 10;7(7). doi: 10.1126/sciadv.abe5905. Print 2021 Feb.
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Causes and consequences of RNA polymerase II stalling during transcript elongation.RNA 聚合酶 II 在转录延伸过程中暂停的原因和后果。
Nat Rev Mol Cell Biol. 2021 Jan;22(1):3-21. doi: 10.1038/s41580-020-00308-8. Epub 2020 Nov 18.
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Condensin complexes: understanding loop extrusion one conformational change at a time.凝聚素复合物：一次一个构象变化，了解环挤出。
转录在分化过程中诱导染色质结构的上下文相关重塑。
PLoS Biol. 2023 Dec 4;21(12):e3002424. doi: 10.1371/journal.pbio.3002424. eCollection 2023 Dec.
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Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase.着丝粒由庇护蛋白定位，驱动姐妹染色单体在后期分离。
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Transcription shapes 3D chromatin organization by interacting with loop extrusion.转录通过与环挤出相互作用来塑造 3D 染色质结构。
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Fold-change of chromatin condensation in yeast is a conserved property.酵母染色质凝聚的变化倍数是一种保守特性。
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