• Open Access

Stress-associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain

Authors

  • Yixing Han,

    1. 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, Shanghai, China
    2. Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    3. Graduate University of Chinese Academy of Sciences, Beijing, China
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    • These authors contributed equally to this work.

  • Dali Han,

    1. 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, Shanghai, China
    2. Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    3. Graduate University of Chinese Academy of Sciences, Beijing, China
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    • These authors contributed equally to this work.

  • Zheng Yan,

    1. 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, Shanghai, China
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  • Jerome D. Boyd-Kirkup,

    1. 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, Shanghai, China
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  • Christopher D. Green,

    1. 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, Shanghai, China
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  • Philipp Khaitovich,

    1. 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, Shanghai, China
    2. Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
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  • Jing-Dong J. Han

    Corresponding author
    • 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, Shanghai, China
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Correspondence

Jing-Dong J. Han, 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. Tel.: 8621 54920458; fax: 8621 54920451; e-mail: jdhan@picb.ac.cn

Summary

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.

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