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Super-Resolution Imaging of Higher-Order Chromatin Structures at Different Epigenomic States in Single Mammalian Cells
Journal article   Open access   Peer reviewed

Super-Resolution Imaging of Higher-Order Chromatin Structures at Different Epigenomic States in Single Mammalian Cells

Jianquan Xu, Hongqiang Ma, Jingyi Jin, Shikhar Uttam, Rao Fu, Yi Huang and Yang Liu
Cell reports (Cambridge), Vol.24(4), pp.873-882
07/24/2018
DOI: 10.1016/j.celrep.2018.06.085
PMCID: PMC6154382
PMID: 30044984
url
https://doi.org/10.1016/j.celrep.2018.06.085View
Published (Version of record) Open Access

Abstract

Histone modifications influence higher-order chromatin structures at individual epigenomic states and chromatin environments to regulate gene expression. However, genome-wide higher-order chromatin structures shaped by different histone modifications remain poorly characterized. With stochastic optical reconstruction microscopy (STORM), we characterized the higher-order chromatin structures at their epigenomic states, categorized into three major types in interphase: histone acetylation marks form spatially segregated nanoclusters, active histone methylation marks form spatially dispersed larger nanodomains, and repressive histone methylation marks form condensed large aggregates. These distinct structural characteristics are also observed in mitotic chromosomes. Furthermore, active histone marks coincide with less compact chromatin and exhibit a higher degree of co-localization with other active marks and RNA polymerase II (RNAP II), while repressive marks coincide with densely packed chromatin and spatially distant from repressive marks and active RNAP II. Taken together, super-resolution imaging reveals three distinct chromatin structures at various epigenomic states, which may be spatially coordinated to impact transcription. [Display omitted] •Histone marks form three distinct types of structures in interphase and during mitosis•Active histone marks coincide with less compact DNA and near active RNA polymerase II•Repressive marks coincide with condensed DNA and distant from active RNA polymerase II Using STORM-based super-resolution microscopy, Xu et al. discover that genome-wide higher-order chromatin structures at various epigenomic states form three types of distinct structures: segregated nanoclusters, dispersed nanodomains, and compact large aggregates. Their spatial relationship with each other and RNA polymerase II suggests spatial coordination that impacts transcription.
chromatin structure histone modification stochastic optical reconstruction microscopy STORM super-resolution imaging

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