Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops.
Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops.
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DOI：
10.26508/lsa.202302101
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发表时间：
2023-10
影响因子：
4.4
通讯作者：
Bickmore, Wendy A.
中科院分区：
文献类型：
--
作者：
Williamson, Iain;Boyle, Shelagh;Grimes, Graeme R.;Friman, Elias T.;Bickmore, Wendy A.
内源性PRC 1介导的染色质致密化和聚簇的polycomb目标基因座是可逆的干扰mESC中添加的1，6己二醇，这可以破坏生物分子的缩合物。多梳阻遏复合物1（PRC 1）强烈影响3D基因组组织，介导局部染色质压缩和靶基因座的聚类。几个PRC 1亚基具有通过体外液-液相分离以及当在细胞中标记和过表达时形成生物分子缩合物的能力。在这里，我们使用1，6-己二醇，它可以破坏液体样冷凝物，检查内源性PRC 1生物分子冷凝物的PRC 1结合位点的本地和染色体范围内的集群的作用。使用成像和染色质免疫沉淀，我们表明PRC 1介导的染色质压实和集群的靶向基因组位点-在不同的长度尺度-可以可逆地破坏添加和随后删除的1，6-己二醇小鼠胚胎干细胞。polycomb结构域和簇的分解和分散不能仅仅归因于在1，6-己二醇处理后通过染色质免疫沉淀检测到的PRC 1占用减少，因为添加2，5-己二醇对结合具有类似的作用，尽管这种醇不干扰PRC 1介导的3D聚类，至少在亚兆和兆尺度上。这些结果表明PRC 1分子之间的弱疏水相互作用可能在polycomb介导的基因组组织中发挥作用。
Endogenous PRC1-mediated chromatin compaction and clustering of polycomb target loci is reversibly perturbed in mESCs by the addition of 1,6 hexanediol, which can disrupt biomolecular condensates. Polycomb repressive complex 1 (PRC1) strongly influences 3D genome organization, mediating local chromatin compaction and clustering of target loci. Several PRC1 subunits have the capacity to form biomolecular condensates through liquid–liquid phase separation in vitro and when tagged and over-expressed in cells. Here, we use 1,6-hexanediol, which can disrupt liquid-like condensates, to examine the role of endogenous PRC1 biomolecular condensates on local and chromosome-wide clustering of PRC1-bound loci. Using imaging and chromatin immunoprecipitation, we show that PRC1-mediated chromatin compaction and clustering of targeted genomic loci—at different length scales—can be reversibly disrupted by the addition and subsequent removal of 1,6-hexanediol to mouse embryonic stem cells. Decompaction and dispersal of polycomb domains and clusters cannot be solely attributable to reduced PRC1 occupancy detected by chromatin immunoprecipitation following 1,6-hexanediol treatment as the addition of 2,5-hexanediol has similar effects on binding despite this alcohol not perturbing PRC1-mediated 3D clustering, at least at the sub-megabase and megabase scales. These results suggest that weak hydrophobic interactions between PRC1 molecules may have a role in polycomb-mediated genome organization.
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影响因子：
30.8
作者：
Schoenfelder S;Sugar R;Dimond A;Javierre BM;Armstrong H;Mifsud B;Dimitrova E;Matheson L;Tavares-Cadete F;Furlan-Magaril M;Segonds-Pichon A;Jurkowski W;Wingett SW;Tabbada K;Andrews S;Herman B;LeProust E;Osborne CS;Koseki H;Fraser P;Luscombe NM;Elderkin S
通讯作者：
Elderkin S
影响因子：
4.4
作者：
Itoh Y;Iida S;Tamura S;Nagashima R;Shiraki K;Goto T;Hibino K;Ide S;Maeshima K
通讯作者：
Maeshima K
影响因子：
8.8
作者：
Rhodes, James D. P.;Feldmann, Angelika;Klose, Robert J.
通讯作者：
Klose, Robert J.
影响因子：
64.8
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
通讯作者：
Narlikar GJ
影响因子：
7.7
作者：
Bajpai G;Amiad Pavlov D;Lorber D;Volk T;Safran S
通讯作者：
Safran S