Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation.
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.
['Cheng|Hao|H|', 'Xuan|Hongwen|H|', 'Green|Christopher D|CD|', 'Han|Yixing|Y|', 'Sun|Na|N|', 'Shen|Hongjie|H|', 'McDermott|Joseph|J|', 'Bennett|David A|DA|', 'Lan|Fei|F|', 'Han|Jing-Dong J|JJ|']
D000107:Acetylation D000375:Aging D000818:Animals D001921:Brain D020869:Gene Expression Profiling D006657:Histones D006801:Humans D007249:Inflammation D051379:Mice D011401:Promoter Regions, Genetic D014158:Transcription, Genetic D059467:Transcriptome
brain inflammation H3K27ac aging gene-body acetylation