Scientists Uncover the Repressive Functions of Histone Acetylation on Inflammaging Related Genes in Brain
Aging is a complex process which interplayed with multiplex factors. During mammalian aging, a low-grade and chronic inflammation was gradually appeared, these inflammation state is termed as “inflammaging” has been known to linked with both neurodegenerative disease and death in elderly people. However, little is known about the underline regulatory process of inflammaging and there has no ideal strategy to prevent inflammaging.
A research team led by Prof. Jing-Dong Jackie HAN from CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences uncovered a new mode of epigenetic regulation of the brain inflammaging genes. The study suggests reversibility of the inflammaging process and a potential new angle for intervention of aging-related brain function decline and neural degenerative diseases.
In this study, researchers generated and analyzed transcriptome and H3K27ac epigenome high throughput sequencing data from human and mouse cortex with different ages. During brain aging, the global acetylation level were decreased, however, besides classical acetylation peaks on promoter, age up-regulated genes contained additional broad gene-body hyper acetylation. These gene-body hyper acetylation decreased in aged samples and correlated with over activation of inflammation related genes during aging. More importantly, restored acetylation on gene-body of inflammation related genes by HDAC inhibitor could attenuated up regulating of these genes in middle aged mice.
Altogether, researchers’ findings revealed opposite regulations by H3K27ac on Age-Up and Age-Down genes and a novel mode of broad gene body H3K27ac in repressing transcription.
This work was mainly contributed by Dr. CHENG Hao and Dr. XUAN Hongwen under the supervision of Prof. Jing-Dong Jackie HAN. The study was collaborated with Prof. LAN Fei at Fudan University and Prof. David Bennett at Rush University.
The research was supported by grants from China Ministry of Science and Technology, National Natural Science Foundation of China, Chinese Academy of Sciences, National Institutes of Health USA and Science and Technology Commission of Shanghai Municipality.
Opposite to acetylation peaks on promoters (right), gene-body hyper acetylation repress gene expression (left).
(Image by Prof Han's team)
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