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Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation

Author

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  • Li Ma

    (University of Southern California)

  • Feng Wang

    (Emory University School of Medicine)

  • Yangping Li

    (Emory University School of Medicine)

  • Jing Wang

    (University of California Los Angeles)

  • Qing Chang

    (University of Southern California)

  • Yuanning Du

    (University of Southern California)

  • Jotham Sadan

    (University of Southern California)

  • Zhen Zhao

    (University of Southern California)

  • Guoping Fan

    (University of California Los Angeles)

  • Bing Yao

    (Emory University School of Medicine)

  • Jian-Fu Chen

    (University of Southern California)

Abstract

How early life experience is translated into storable epigenetic information leading to behavioral changes remains poorly understood. Here we found that Zika virus (ZIKV) induced-maternal immune activation (MIA) imparts offspring with anxiety- and depression-like behavior. By integrating bulk and single-nucleus RNA sequencing (snRNA-seq) with genome-wide 5hmC (5-hydroxymethylcytosine) profiling and 5mC (5-methylcytosine) profiling in prefrontal cortex (PFC) of ZIKV-affected male offspring mice, we revealed an overall loss of 5hmC and an increase of 5mC levels in intragenic regions, associated with transcriptional changes in neuropsychiatric disorder-related genes. In contrast to their rapid initiation and inactivation in normal conditions, immediate-early genes (IEGs) remain a sustained upregulation with enriched expression in excitatory neurons, which is coupled with increased 5hmC and decreased 5mC levels of IEGs in ZIKV-affected male offspring. Thus, MIA induces maladaptive methylome remodeling in brain and selectively regulates neuronal activity gene methylation linking to emotional behavioral abnormalities in offspring.

Suggested Citation

  • Li Ma & Feng Wang & Yangping Li & Jing Wang & Qing Chang & Yuanning Du & Jotham Sadan & Zhen Zhao & Guoping Fan & Bing Yao & Jian-Fu Chen, 2023. "Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43497-4
    DOI: 10.1038/s41467-023-43497-4
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    1. Zhi-Hui Yang & Xin Cai & Chu-Yi Zhang & Qing Zhang & Miao Li & Zhong-Li Ding & Yingqi Guo & Guolan Ma & Chao-Hao Yang & Lei Guo & Hong Chang & Chuang Wang & Ming Li & Xiao Xiao, 2024. "NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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