Frontiers in Neuroscience (Apr 2022)

Redistribution of Histone Marks on Inflammatory Genes Associated With Intracerebral Hemorrhage-Induced Acute Brain Injury in Aging Rats

  • Qin Zhang,
  • Wei-lin Kong,
  • Jun-Jie Yuan,
  • Qiong Chen,
  • Chang-Xiong Gong,
  • Liang Liu,
  • Fa-Xiang Wang,
  • Jia-Cheng Huang,
  • Guo-Qiang Yang,
  • Kai Zhou,
  • Rui Xu,
  • Xiao-Yi Xiong,
  • Xiao-Yi Xiong,
  • Xiao-Yi Xiong,
  • Qing-Wu Yang

DOI
https://doi.org/10.3389/fnins.2022.639656
Journal volume & issue
Vol. 16

Abstract

Read online

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.

Keywords