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通过相分离实现 Polycomb 抑制复合物 1 凝聚物的组装和调控原理。

Principles of assembly and regulation of condensates of Polycomb repressive complex 1 through phase separation.

机构信息

Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA.

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.

出版信息

Cell Rep. 2023 Oct 31;42(10):113136. doi: 10.1016/j.celrep.2023.113136. Epub 2023 Sep 26.

DOI:10.1016/j.celrep.2023.113136
PMID:37756159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10862386/
Abstract

Polycomb repressive complex 1 (PRC1) undergoes phase separation to form Polycomb condensates that are multi-component hubs for silencing Polycomb target genes. In this study, we demonstrate that formation and regulation of PRC1 condensates are consistent with the scaffold-client model, where the Chromobox 2 (CBX2) protein behaves as the scaffold while the other PRC1 proteins are clients. Such clients induce a re-entrant phase transition of CBX2 condensates. The composition of the multi-component PRC1 condensates (1) determines the dynamic properties of the scaffold protein; (2) selectively promotes the formation of CBX4-PRC1 condensates while dissolving condensates of CBX6-, CBX7-, and CBX8-PRC1; and (3) controls the enrichment of CBX4-, CBX7-, and CBX8-PRC1 in CBX2-PRC1 condensates and the exclusion of CBX6-PRC1 from CBX2-PRC1 condensates. Our findings uncover how multi-component PRC1 condensates are assembled via an intricate scaffold-client mechanism whereby the properties of the PRC1 condensates are sensitively regulated by its composition and stoichiometry.

摘要

多梳抑制复合物 1（PRC1）发生液-液相分离形成多梳抑制复合物浓缩物，是沉默多梳抑制复合物靶基因的多组分中心。在这项研究中，我们证明了 PRC1 浓缩物的形成和调节与支架-客户模型一致，其中 Chromobox 2（CBX2）蛋白作为支架，而其他 PRC1 蛋白作为客户。这些客户诱导 CBX2 浓缩物的再入相转变。多组分 PRC1 浓缩物的组成：1）决定支架蛋白的动态特性；2）选择性促进 CBX4-PRC1 浓缩物的形成，同时溶解 CBX6-PRC1、CBX7-PRC1 和 CBX8-PRC1 浓缩物；3）控制 CBX4-PRC1、CBX7-PRC1 和 CBX8-PRC1 在 CBX2-PRC1 浓缩物中的富集和 CBX6-PRC1 从 CBX2-PRC1 浓缩物中的排除。我们的发现揭示了多组分 PRC1 浓缩物如何通过复杂的支架-客户机制组装，其中 PRC1 浓缩物的性质通过其组成和化学计量比敏感地调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/0c8e11ba6689/nihms-1941856-f0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/de0a8eb1665f/nihms-1941856-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/7bd1f664770b/nihms-1941856-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/0c8e11ba6689/nihms-1941856-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/cb09b87e6f57/nihms-1941856-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/de0a8eb1665f/nihms-1941856-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/7bd1f664770b/nihms-1941856-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/10862386/0c8e11ba6689/nihms-1941856-f0008.jpg

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