Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain; Institute of Photonic Sciences (ICFO), The Barcelona Institute of Science and Technology (BIST), Castelldefels, 08860 Barcelona, Spain.
Department of Chemistry, 1021 Silver Center, 100 Washington Square East, New York University, New York, NY 10003, USA.
Cell Rep. 2021 Jan 12;34(2):108614. doi: 10.1016/j.celrep.2020.108614.
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.
核小体在体内形成异质群体，称为 clutches。与神经祖细胞（NPCs）相比，小鼠胚胎干细胞（ESCs）中的 clutches 更小且密度更低。通过对多能性 Pou5f1 基因进行粗粒化建模，我们表明 ESC 和 NPC 之间全基因组 clutch 差异可以在单个基因座上重现。NPC 中更大的 clutch 形成与 Pou5f1 纤维的压缩和核小体间接触概率的变化有关。通过单分子跟踪（SMT），我们进一步表明核心组蛋白 H2B 是动态的，其局部迁移性与染色质纤维的结构特征有关。与 NPCs 相比，H2B 在 ESCs 中更不稳定，并且探索更大的区域。连接组蛋白 H1 的量对局部 H2B 动力学有重要影响。我们的研究结果对于核小体组织和 H2B 动力学如何调节基因活性和细胞身份具有重要意义。
