title: Stress-associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain.
abstract: Epigenetic modifications are critical determinants of cellular and developmental states. Epigenetic changes, such as decreased H3K27me3 histone methylation on insulin/IGF1 genes, have been previously shown to modulate lifespan through gene expression regulation. However, global epigenetic changes during aging and their biological functions, if any, remain elusive. Here, we examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) at the whole genome level. Through integrative analysis of the ChIP-seq profiles with gene expression data, we found that H3K4me2 increased at promoters and enhancers globally during postnatal development and aging, and those that correspond to gene expression changes in cis are enriched for stress responses, such as the DNA damage response. This suggests that metabolic and environmental stresses experienced by an organism are associated with the progressive opening of chromatin. In support of this, we also observed increased expression of two H3K4 methyltransferases, SETD7 and DPY30, in aged macaque brain.
authors.affiliation: Chinese Academy of Sciences Key laboratory for Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Han
authors.forename: Dali
authors.initials: D
authors.lastname: Han
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Jerome D
authors.initials: JD
authors.lastname: Boyd-Kirkup
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Green
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D008745:Methylation; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D002843:Chromatin; D006657:Histones; D011496:Protein Methyltransferases