AUTHOR=Zhang Qin , Kong Wei-lin , Yuan Jun-Jie , Chen Qiong , Gong Chang-Xiong , Liu Liang , Wang Fa-Xiang , Huang Jia-Cheng , Yang Guo-Qiang , Zhou Kai , Xu Rui , Xiong Xiao-Yi , Yang Qing-Wu TITLE=Redistribution of Histone Marks on Inflammatory Genes Associated With Intracerebral Hemorrhage-Induced Acute Brain Injury in Aging Rats JOURNAL=Frontiers in Neuroscience VOLUME=16 YEAR=2022 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.639656 DOI=10.3389/fnins.2022.639656 ISSN=1662-453X ABSTRACT=

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.