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Visualization of the dynamic interaction between nucleosomal histone H3K9 tri-methylation and HP1α chromodomain in living cells
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2022-06-20 , DOI: 10.1016/j.chembiol.2022.05.006
Kazuki Sasaki 1 , Michihiro Suzuki 2 , Takeshi Sonoda 3 , Tilman Schneider-Poetsch 1 , Akihiro Ito 4 , Motoki Takagi 5 , Shinya Fujishiro 6 , Yoshihiro Sohtome 7 , Kosuke Dodo 7 , Takashi Umehara 8 , Hiroyuki Aburatani 9 , Kazuo Shin-Ya 10 , Yoichi Nakao 11 , Mikiko Sodeoka 7 , Minoru Yoshida 12
Affiliation  

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 HP1α chromodomain (HP1αCD), 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 HP1αCD 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 HP1α.



中文翻译:

活细胞中核小体组蛋白 H3K9 三甲基化与 HP1α 染色质域之间动态相互作用的可视化

组蛋白赖氨酸甲基化是一种可以控制基因表达的表观遗传标记。特别是,H3K9me3 通过调节染色质结构有助于转录抑制。成功的有丝分裂进程需要正确计时染色质结构变化,包括表观遗传标记。然而,关于活细胞中组蛋白修饰的时空信息仍然有限。在这项研究中,我们基于与 H3K9me3 结合的 HP1α 染色质域 (HP1αCD) 创建了一种基于 FRET 的活细胞成像探针。该探针被整合到染色质中,并且在用组蛋白甲基转移酶抑制剂处理后发射比降低,表明它成功地追踪了 H3K9me3 的动态变化。进入有丝分裂后,探针的发射率随着 H3K9me3 的增加而瞬时增加,然后表现出逐步下降,可能是由于 H3S10 的磷酸化和 H3K9me3 的去甲基化导致的 HP1αCD 结合丧失。该探针将成为检测与 HP1α 相关的染色质结构动态变化的有用工具。

更新日期:2022-06-20
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