Di Nisio Elena, Lupo Giuseppe, Licursi Valerio, Negri Rodolfo
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy.
Institute of Molecular Biology and Pathology, National Research Counsil (IBPM-CNR), Rome, Italy.
Front Genet. 2021 Mar 30;12:639602. doi: 10.3389/fgene.2021.639602. eCollection 2021.
Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors. Here, we review the role of histone lysine methylation changes in regulating the response to radiation-induced genotoxic damage in mammalian cells. We also discuss the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) and the effects of the modulation of their expression and/or the pharmacological inhibition of their activity on the radio-sensitivity of different cell lines. Finally, we provide a bioinformatic analysis of published datasets showing how the mRNA levels of known HMTs and HDMs are modulated in different cell lines by exposure to different irradiation conditions.
真核生物基因组缠绕在核小体周围,并组织成不同层次的染色质结构。染色质组织在调节所有涉及DNA-蛋白质相互作用的细胞过程中起着关键作用,如DNA转录、复制、重组和修复。组蛋白翻译后修饰(HPTMs)在染色质调节中发挥着重要作用,充当一种复杂的分子密码,由HPTM特异性效应器进行解读。在此,我们综述组蛋白赖氨酸甲基化变化在调节哺乳动物细胞对辐射诱导的基因毒性损伤反应中的作用。我们还讨论了组蛋白甲基转移酶(HMTs)和组蛋白去甲基化酶(HDMs)的作用,以及它们表达的调节和/或其活性的药理学抑制对不同细胞系放射敏感性的影响。最后,我们对已发表的数据集进行了生物信息学分析,展示了已知HMTs和HDMs的mRNA水平在不同细胞系中如何受到不同照射条件的调节。