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Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11681-E11690. doi: 10.1073/pnas.1811818115. Epub 2018 Nov 26.

Coordinated histone modifications and chromatin reorganization in a single cell revealed by FRET biosensors.

Author information

1
College of Bioengineering, Chongqing University, 400044 Chongqing, China.
2
Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093.
3
Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093; kalu@eng.ucsd.edu wyl@cqu.edu.cn shuchien@ucsd.edu yiw015@eng.ucsd.edu.
4
Infectious & Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.
5
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, NY 10461.
6
Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, NY 10461.
7
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.
8
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
9
Institute of Genomic Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
10
College of Bioengineering, Chongqing University, 400044 Chongqing, China; kalu@eng.ucsd.edu wyl@cqu.edu.cn shuchien@ucsd.edu yiw015@eng.ucsd.edu.

Abstract

The dramatic reorganization of chromatin during mitosis is perhaps one of the most fundamental of all cell processes. It remains unclear how epigenetic histone modifications, despite their crucial roles in regulating chromatin architectures, are dynamically coordinated with chromatin reorganization in controlling this process. We have developed and characterized biosensors with high sensitivity and specificity based on fluorescence resonance energy transfer (FRET). These biosensors were incorporated into nucleosomes to visualize histone H3 Lys-9 trimethylation (H3K9me3) and histone H3 Ser-10 phosphorylation (H3S10p) simultaneously in the same live cell. We observed an anticorrelated coupling in time between H3K9me3 and H3S10p in a single live cell during mitosis. A transient increase of H3S10p during mitosis is accompanied by a decrease of H3K9me3 that recovers before the restoration of H3S10p upon mitotic exit. We further showed that H3S10p is causatively critical for the decrease of H3K9me3 and the consequent reduction of heterochromatin structure, leading to the subsequent global chromatin reorganization and nuclear envelope dissolution as a cell enters mitosis. These results suggest a tight coupling of H3S10p and H3K9me3 dynamics in the regulation of heterochromatin dissolution before a global chromatin reorganization during mitosis.

KEYWORDS:

FRET biosensors; chromatin reorganization; histone modifications

PMID:
30478057
DOI:
10.1073/pnas.1811818115

Conflict of interest statement

Conflict of interest statement: Yingxiao Wang and S.L. are scientific cofounders of Cell E&G Inc. However, these financial interests do not affect the design, conduct, or reporting of this research.

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