Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation

Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):7611-7616. doi: 10.1073/pnas.1800656115. Epub 2018 Jul 2.


Brain "inflammaging," a low-grade and chronic inflammation, is a major hallmark for aging-related neurodegenerative diseases. Here, by profiling H3K27ac and gene expression patterns in human and mouse brains, we found that age-related up-regulated (Age-Up) and down-regulated (Age-Down) genes have distinct H3K27ac patterns. Although both groups show promoter H3K27ac, the Age-Up genes, enriched for inflammation-related functions, are additionally marked by broad H3K27ac distribution over their gene bodies, which is progressively reduced during aging. Age-related gene expression changes can be predicted by gene-body H3K27ac level. Contrary to the presumed transcription activation function of promoter H3K27ac, we found that broad gene-body hyper H3K27ac suppresses overexpression of inflammaging genes. Altogether, our findings revealed opposite regulations by H3K27ac of Age-Up and Age-Down genes and a mode of broad gene-body H3K27ac in repressing transcription.

Keywords: H3K27ac; aging; brain; gene-body acetylation; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Brain / metabolism*
  • Gene Expression Profiling
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Mice
  • Promoter Regions, Genetic*
  • Transcription, Genetic*
  • Transcriptome*


  • Histones