2022Zhang NucleosomeTrasition
Citation
Molecular Organization of the Early Stages of Nucleosome Phase Separation Visualized by Cryo-Electron Tomography, Meng Zhang, César Díaz-Celis, Bibiana Onoa, Cristhian Cañari-Chumpitaz, Katherinne I. Requejo, Jianfang Liu, Michael Vien, Eva Nogales, Gang Ren, and Carlos Bustamante, Molecular Cell, (2022), 18;82(16):3000-3014.e9; PMID: 35907400 DOI: 10.1016/j.molcel.2022.06.032
Abstract
It has been proposed that the intrinsic property of nucleosome arrays to undergo liquid-liquid phase separation (LLPS) in vitro is responsible for chromatin domain organization in vivo. However, understanding nucleosomal LLPS has been hindered by the challenge to characterize the structure of the resulting heterogeneous condensates. We used cryo-electron tomography and deep-learning-based 3D reconstruction/segmentation to determine the molecular organization of condensates at various stages of LLPS. We show that nucleosomal LLPS involves a two-step process: a spinodal decomposition process yielding irregular condensates, followed by their unfavorable conversion into more compact, spherical nuclei that grow into larger spherical aggregates through accretion of spinodal materials or by fusion with other spherical condensates. Histone H1 catalyzes more than 10-fold the spinodal-to-spherical conversion. We propose that this transition involves exposure of nucleosome hydrophobic surfaces causing modified inter-nucleosome interactions. These results suggest a physical mechanism by which chromatin may transition from interphase to metaphase structures.
Keywords
Cryo-ET, single molecule structure, individual-particle cryo-electron tomography, IPET, nucleosome array, phase transition, aggregation
Paper links
https://pubmed.ncbi.nlm.nih.gov/35907400/
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