Transcription-mediated supercoiling regulates genome folding and loop formation.
Transcription-mediated supercoiling regulates genome folding and loop formation.
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DOI：
10.1016/j.molcel.2021.06.009
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发表时间：
2021-08-05
期刊：
影响因子：
16
通讯作者：
Cosma, Maria Pia
中科院分区：
文献类型：
--
作者：
Victoria Neguembor, Maria;Martin, Laura;Castells-Garcia, Alvaro;Aurelio Gomez-Garcia, Pablo;Vicario, Chiara;Carnevali, Davide;Abed, Jumana AlHaj;Granados, Alba;Sebastian-Perez, Ruben;Sottile, Francesco;Solon, Jerome;Wu, Chao-ting;Lakadamyali, Melike;Cosma, Maria Pia
染色质纤维折叠成环，但控制环挤压的机制仍然知之甚少。使用超分辨率显微镜，我们看到完整细胞核中的环是由DNA突出的内聚蛋白复合物支架形成的。RNA聚合酶II修饰环的顶部，与黏结蛋白物理分离。在染色体上增加内聚蛋白的负载时，增加的环导致核边缘的层合蛋白和染色质混合的破坏，染色质在细胞核内均匀分布。通过转录或拓扑异构酶抑制改变超卷曲会抵消染色质混合，增加染色质凝聚，破坏环的形成，并导致染色质上的内聚蛋白分布和迁移性的改变。总之，转录产生的负超旋是体内环形成的重要调节因子。染色质环形成的机制由内聚物介导的挤压仍然部分未知。利用超分辨率成像技术，Neguembor等人可视化了完整细胞核中纳米级环是如何组织的，并表明转录产生的超卷曲调节了体内环的形成。
The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top of the loops and is physically segregated from cohesin. Augmented looping upon increased loading of cohesin on chromosomes causes disruption of Lamin at the nuclear rim and chromatin blending, a homogeneous distribution of chromatin within the nucleus. Altering supercoiling via either transcription or topoisomerase inhibition counteracts chromatin blending, increases chromatin condensation, disrupts loop formation, and leads to altered cohesin distribution and mobility on chromatin. Overall, negative supercoiling generated by transcription is an important regulator of loop formation in vivo. The mechanisms underlying chromatin loop formation by cohesin-mediated extrusion are still partially unknown. Using super-resolution imaging, Neguembor et al. visualize how loops are organized at the nanoscale level in intact nuclei and show that transcriptionally generated supercoiling regulates loop formation in vivo.
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影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
7.7
作者：
Barutcu, A. Rasim;Blencowe, Benjamin J.;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
4.6
作者：
Andronov L;Orlov I;Lutz Y;Vonesch JL;Klaholz BP
通讯作者：
Klaholz BP
影响因子：
16
作者：
Cardozo Gizzi, Andres M.;Cattoni, Diego, I;Nollmann, Marcelo
通讯作者：
Nollmann, Marcelo
DOI：
10.1126/science.1259418
发表时间：
2015-02-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arner E;Daub CO;Vitting-Seerup K;Andersson R;Lilje B;Drabløs F;Lennartsson A;Rönnerblad M;Hrydziuszko O;Vitezic M;Freeman TC;Alhendi AM;Arner P;Axton R;Baillie JK;Beckhouse A;Bodega B;Briggs J;Brombacher F;Davis M;Detmar M;Ehrlund A;Endoh M;Eslami A;Fagiolini M;Fairbairn L;Faulkner GJ;Ferrai C;Fisher ME;Forrester L;Goldowitz D;Guler R;Ha T;Hara M;Herlyn M;Ikawa T;Kai C;Kawamoto H;Khachigian LM;Klinken SP;Kojima S;Koseki H;Klein S;Mejhert N;Miyaguchi K;Mizuno Y;Morimoto M;Morris KJ;Mummery C;Nakachi Y;Ogishima S;Okada-Hatakeyama M;Okazaki Y;Orlando V;Ovchinnikov D;Passier R;Patrikakis M;Pombo A;Qin XY;Roy S;Sato H;Savvi S;Saxena A;Schwegmann A;Sugiyama D;Swoboda R;Tanaka H;Tomoiu A;Winteringham LN;Wolvetang E;Yanagi-Mizuochi C;Yoneda M;Zabierowski S;Zhang P;Abugessaisa I;Bertin N;Diehl AD;Fukuda S;Furuno M;Harshbarger J;Hasegawa A;Hori F;Ishikawa-Kato S;Ishizu Y;Itoh M;Kawashima T;Kojima M;Kondo N;Lizio M;Meehan TF;Mungall CJ;Murata M;Nishiyori-Sueki H;Sahin S;Nagao-Sato S;Severin J;de Hoon MJ;Kawai J;Kasukawa T;Lassmann T;Suzuki H;Kawaji H;Summers KM;Wells C;FANTOM Consortium;Hume DA;Forrest AR;Sandelin A;Carninci P;Hayashizaki Y
通讯作者：
Hayashizaki Y