Kazuki Sasaki, Michihiro Suzuki, Takeshi Sonoda, Tilman Schneider-Poetsch, Akihiro Ito, Motoki Takagi, Shinya Fujishiro, Yoshihiro Sohtome, Kosuke Dodo, Takashi Umehara, Hiroyuki Aburatani, Kazuo Shin-Ya, Yoichi Nakao, Mikiko Sodeoka, Minoru Yoshida (2022) Visualization of the dynamic interaction between nucleosomal histone H3K9 tri-methylation and HP1alpha chromodomain in living cells., Cell chemical biology, Volume 29, Number 7, pp. 1153-1161.e5
Published in 2022 Jul 21 (Electronic publication in June 20, 2022, midnight )
(Abstract) Histone lysine methylation is an epigenetic mark that can control gene expression. In particular, H3K9me3 contributes to transcriptional repression by regulating chromatin structure. Successful mitotic progression requires correct timing of chromatin structure changes, including epigenetic marks. However, spatiotemporal information on histone modifications in living cells remains limited. In this study, we created an FRET-based probe for live-cell imaging based on the HP1alpha chromodomain (HP1alphaCD), which binds to H3K9me3. The probe was incorporated into chromatin and the emission ratio decreased after treatment with histone methyltransferase inhibitors, indicating that it successfully traced dynamic changes in H3K9me3. Upon entry into mitosis, the probe's emission ratio transiently increased with a concomitant increase in H3K9me3, then exhibited a stepwise decrease, probably due to loss of HP1alphaCD binding caused by phosphorylation of H3S10 and demethylation of H3K9me3. This probe will be a useful tool for detecting dynamic changes in chromatin structure associated with HP1alpha.(MeSH Terms)