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

Qin Peng, Shaoying Lu, Yuxin Shi, Yijia Pan, Praopim Limsakul, Andrei V. Chernov, Juhui Qiu, Xiaoqi Chai, Yiwen Shi, Pengzhi Wang, Yanmin Ji, Yi Shuan J. Li, Alex Y. Strongin, Vladislav V. Verkhusha, Carlos Izpisua Belmonte, Bing Ren, Yuanliang Wang, Shu Chien, Yingxiao Wang

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E11681-E11690
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 11 2018


  • Chromatin reorganization
  • FRET biosensors
  • Histone modifications

ASJC Scopus subject areas

  • General


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