Epigenetic roles of DNA adenine methylation in stress response

DNA 腺嘌呤甲基化在应激反应中的表观遗传作用

基本信息

  • 批准号:
    10323656
  • 负责人:
  • 金额:
    $ 39.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-04-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary Methylation on the DNA adenine, N6-methyladenine (6mA) that enriched in the bacteria genome, was recently found in the Drosophila and mammalian genomes. 6mA is dynamically regulated during embryonic development and could play epigenetic roles in regulating gene and transposon expression. However, the roles of 6mA in mammalian brains remain largely unknown. Our preliminary study highlights that 6mA, and its molecular machinery, is required for proper neurodevelopment in Drosophila brains. Preliminary data consistently demonstrated a dynamic regulation of 6mA during postnatal mouse brain and human embryoid body development. Environmental chronic stress induces dynamic alteration of 6mA in mouse brains, in the loci highly correlated with depression. The complex changes in postnatal brain development due to the epigenetic alteration could account for the altered stress response and many mental illnesses, the molecular mechanisms connecting these processes remain unclear. The involvement of 6mA and its putative machinery in brain development and stress response makes them an attractive causal mechanism in these connected processes. However, there is little research precisely examining the brain region-specific and neuronal cell type-specific 6mA dynamics and their epigenetic roles during brain development. Furthermore, the lack of knowledge regarding the 6mA methyltransferases (“writers”) and its binding proteins (“readers”) in the mammalian genome hinders our further understanding of their precise epigenetic roles in brain development and stress response. Based on this work, we hypothesize that 6mA and its molecular machinery play crucial roles in mammalian brain development, and their dysregulation contributes to altered stress response in the brain. We will first use established genome-wide 6mA mapping tools to identify brain region-specific and cell type-specific differentially 6mA methylated regions (D6AMRs) during mouse postnatal development and correlate these data with global transcriptome analysis to pinpoint the detailed and precise epigenetic roles of 6mA in these processes (Aim 1). We will then define 6mA putative methyltransferases “writers” in the mammalian genome and modulate their expression in vivo to test their roles in development-related stress response through 6mA regulation in excitatory and inhibitory neurons (Aim 2). Our data suggest 6mA could potentially antagonize or recruit hypoxia-induced factor-1 (Hif1) and Drosophila Polycomb (Pc), respectively. Based on these results, we will determine the interplay of Hif1 and mammalian Polycomb proteins with 6mA and their roles in development-related stress response at the neuronal levels as well (Aim 3). Findings of this study will provide novel mechanistic insights of 6mA in brain development and its related stress response and are likely to discover new molecular targets with important clinical and translational implications in mental illnesses.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Bing Yao其他文献

Bing Yao的其他文献

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{{ truncateString('Bing Yao', 18)}}的其他基金

Use of CRISPR/Cas9 to Treat Huntington Disease
使用 CRISPR/Cas9 治疗亨廷顿病
  • 批准号:
    10400202
  • 财政年份:
    2021
  • 资助金额:
    $ 39.03万
  • 项目类别:
Use of CRISPR/Cas9 to Treat Huntington Disease
使用 CRISPR/Cas9 治疗亨廷顿病
  • 批准号:
    10374293
  • 财政年份:
    2021
  • 资助金额:
    $ 39.03万
  • 项目类别:
Epigenetic roles of DNA adenine methylation in stress response
DNA 腺嘌呤甲基化在应激反应中的表观遗传作用
  • 批准号:
    10084319
  • 财政年份:
    2019
  • 资助金额:
    $ 39.03万
  • 项目类别:
Epigenetic roles of DNA adenine methylation in stress response
DNA 腺嘌呤甲基化在应激反应中的表观遗传作用
  • 批准号:
    9896873
  • 财政年份:
    2019
  • 资助金额:
    $ 39.03万
  • 项目类别:
Epigenetic roles of DNA adenine methylation in Alzheimer's Disease
DNA 腺嘌呤甲基化在阿尔茨海默病中的表观遗传学作用
  • 批准号:
    10618183
  • 财政年份:
    2019
  • 资助金额:
    $ 39.03万
  • 项目类别:
Epigenetic roles of DNA adenine methylation in Alzheimer's Disease
DNA 腺嘌呤甲基化在阿尔茨海默病中的表观遗传学作用
  • 批准号:
    10383679
  • 财政年份:
    2019
  • 资助金额:
    $ 39.03万
  • 项目类别:
Epigenetic roles of DNA adenine methylation in stress response
DNA 腺嘌呤甲基化在应激反应中的表观遗传作用
  • 批准号:
    10542665
  • 财政年份:
    2019
  • 资助金额:
    $ 39.03万
  • 项目类别:
Hypothalamic MANF and food-intake activity
下丘脑 MANF 和食物摄入活动
  • 批准号:
    9533710
  • 财政年份:
    2017
  • 资助金额:
    $ 39.03万
  • 项目类别:
Longitudinal Assessment of Spinal Cord Structural Plasticity using DTI in SCI Patients
使用 DTI 对 SCI 患者脊髓结构可塑性进行纵向评估
  • 批准号:
    9221374
  • 财政年份:
    2016
  • 资助金额:
    $ 39.03万
  • 项目类别:

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腺嘌呤核苷酸转位酶在慢性阻塞性肺病(COPD)线粒体功能相关衰老中的作用
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  • 批准号:
    10794933
  • 财政年份:
    2022
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使用 FRET 开发 miRNA 和腺嘌呤甲基转移酶的诺贝尔检测方法
  • 批准号:
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  • 财政年份:
    2021
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健康老龄化和阿尔茨海默病脑细胞 DNA 腺嘌呤甲基化的批判性评估
  • 批准号:
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    2020
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    10226235
  • 财政年份:
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