Mesoscale Modeling and Single-Nucleosome Tracking Reveal Remodeling of Clutch Folding and Dynamics in Stem Cell Differentiation.
Mesoscale Modeling and Single-Nucleosome Tracking Reveal Remodeling of Clutch Folding and Dynamics in Stem Cell Differentiation.
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DOI：
10.1016/j.celrep.2020.108614
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发表时间：
2021-01-12
期刊：
影响因子：
8.8
通讯作者：
Lakadamyali M
中科院分区：
文献类型：
--
作者：
Gómez-García PA;Portillo-Ledesma S;Neguembor MV;Pesaresi M;Oweis W;Rohrlich T;Wieser S;Meshorer E;Schlick T;Cosma MP;Lakadamyali M
核小体在体内形成异质群，称为离合器。与神经祖细胞（NPC）相比，小鼠胚胎干细胞（ESC）中的细胞团较小且密度较低。使用多能性Pou 5 f1基因的粗粒度建模，我们表明，胚胎干细胞和NPC之间的全基因组离合器差异可以在一个单一的基因位点复制。NPC中较大的离合器形成与Pou 5 f1纤维的压实和核小体间接触概率的变化有关。使用单分子跟踪（SMT），我们进一步表明，核心组蛋白H2 B是动态的，其局部流动性与染色质纤维的结构特征。与NPC相比，H2 B不太稳定，并且在ESC中探索更大的区域。接头组蛋白H1的量严重影响局部H2 B动力学。我们的研究结果对于核小体组织和H2 B动力学如何有助于调节基因活性和细胞身份具有重要意义。Gómez-García等人表明Pou 5 f1基因折叠成核小体离合器，分化细胞中的离合器比干细胞中的离合器大。这些离合器变化伴随着分化细胞中增强的等级循环。H2 B动力学是细胞类型特异性的，与离合器模式相关，并由连接体组蛋白H1调节。
Nucleosomes form heterogeneous groups in vivo, named clutches. Clutches are smaller and less dense in mouse embryonic stem cells (ESCs) compared to neural progenitor cells (NPCs). Using coarse-grained modeling of the pluripotency Pou5f1 gene, we show that the genome-wide clutch differences between ESCs and NPCs can be reproduced at a single gene locus. Larger clutch formation in NPCs is associated with changes in the compaction and internucleosome contact probability of the Pou5f1 fiber. Using single-molecule tracking (SMT), we further show that the core histone protein H2B is dynamic, and its local mobility relates to the structural features of the chromatin fiber. H2B is less stable and explores larger areas in ESCs compared to NPCs. The amount of linker histone H1 critically affects local H2B dynamics. Our results have important implications for how nucleosome organization and H2B dynamics contribute to regulate gene activity and cell identity. Gómez-García et al. show that the Pou5f1 gene folds into nucleosome clutches, with larger clutches in differentiated cells than in stem cells. These clutch changes are accompanied by enhanced hierarchical looping in differentiated cells. H2B dynamics is cell-type specific, correlates with clutch patterns, and is regulated by linker histone H1.
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DOI：
10.1073/pnas.1816424116
发表时间：
2019-03-12
影响因子：
11.1
作者：
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Fierz B
影响因子：
64.5
作者：
Bandaria JN;Qin P;Berk V;Chu S;Yildiz A
通讯作者：
Yildiz A
DOI：
10.1073/pnas.1315872111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Collepardo-Guevara, Rosana;Schlick, Tamar
通讯作者：
Schlick, Tamar