The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation

Abstract

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.

Multi-omics Analysis of Dsup Expressing Human Cells Reveals Open Chromatin Architectural Dynamics Underyling Radioprotection

“…As these marks are typically associated with bivalently poised promoters such as those involved in differentiation and are either silenced or have low transcriptional activity as a result of PRC2 repression 27, 101, 102 , we next set out to probe whether Dsup induction would promote similar epigenetic changes. In addition, we also tracked changes in these epigenetic marks in response to irradiation as fluctuations in opening and closing of chromatin regions following irradiation and DNA damage have been demonstrated such as H3K4me3 removal and increased H3K27me3 deposition via EZH2 around double stranded breaks 103,104 .…”

“…This pattern of opening and closing of peaks appears to be in general agreement with our analysis of gene expression dynamics over time with more downregulated genes appearing at the 6hr timepoint as well. Closing of chromatin post-irradiation has also been well documented as mammalian cells will modulate histone PTMs around the sites of damage to facilitate a repressive chromatin state that limits local transcription so that the steps necessary to begin DNA damage repair can proceed first 104 . Although chromatin accessibility in our dataset were generally stable like that of Nalm6 HMGN1-OE cells, the nuances we observed in opening and closing chromatin state dynamics could be due to our constitutive expression of Dsup over several passages while Mowery et al looked at chromatin state dynamics 6hrs after induction of HMGN1 over expression.…”

The Advances in Epigenetics for Cancer Radiotherapy

“…Bulleted lists look like this: It has been widely reported that radiation has a series of effects on histone modification in tumor cells and normal cells [ 48 ]. H3K27me3 is related to chromatin condensation, which affects DNA double-strand breaks (DSB) repair.…”

Editorial: The Genetic and Epigenetic Bases of Cellular Response to Ionizing Radiation

“…Differential epigenetic changes caused by radiation exposure correlated with cell cycle, DNA repair, and apoptosis (Antwih et al, 2013). Histone modification such as phosphorylation, methylation, and acetylation is well known to play a key role in DNA repair mechanism responding to radiation exposure (Di Nisio et al, 2021). In addition, epigenetic changes regulated by radiation exposure can be governed by the mobilization of Transposon Elements (Yushkova).…”