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Cell Rep. 2018 Jul 24;24(4):873-882. doi: 10.1016/j.celrep.2018.06.085.

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

Author information

1
Biomedical Optical Imaging Laboratory, Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA.
2
Biomedical Optical Imaging Laboratory, Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA; School of Medicine, Tsinghua University, No.1 Tsinghua Yuan, Haidian District, Beijing 100084, China.
3
Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
4
Biomedical Optical Imaging Laboratory, Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA; College of Chemical Engineering, Northeast Electric Power University, Jilin City, Jilin Province 132012, China.
5
Magee-Women's Research Institute, University of Pittsburgh Cancer Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
6
Biomedical Optical Imaging Laboratory, Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: liuy@pitt.edu.

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.

KEYWORDS:

STORM; chromatin structure; histone modification; stochastic optical reconstruction microscopy; super-resolution imaging

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