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Dnmt2调控精子tsRNA介导父代表观遗传印记信息形成的机制研究
结题报告
批准号:
81971460
项目类别:
面上项目
资助金额:
60.0 万元
负责人:
张云芳
依托单位:
学科分类:
生殖系统/围生医学/新生儿疾病研究新技术与新方法
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张云芳
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中文摘要
传统观点认为,性状遗传的基础是DNA序列编码的基因。但是,证据表明环境、饮食等引起的获得性性状可通过精子的表观遗传学印记信息载体传递给子代。申请人前期发现:精子tsRNA及其RNA修饰可作为表观遗传信息载体介导父代高脂饮食诱导的代谢紊乱疾病向子代传递,而tRNA甲基转移酶-DNMT2调控了父代印记信息的形成,参与了精子RNA介导的获得性代谢紊乱疾病的遗传调控(Science, 2016; Nature Cell Biology, 2018)。然而,父代高脂饮食引起的表观遗传印记信息是如何在精子中形成的?DNMT2是如何进行调控的?还不清楚。针对以上问题,申请人拟通过DNMT2基因敲除小鼠,联合多种分子生物学和细胞生物学方法,从精子tsRNA介导的表观遗传印记信息形成的角度深入阐析父代精子RNA介导获得性遗传的分子机制,以期为指导优生优以及今后个体化精准医疗提供更全面的理论基础。
英文摘要
Traditional view believed that the heritable traits are coded by the genes that determined by DNA sequence. However, more and more evidences showed that some acquired traits that induced by the environment exposure and changed diet also could be delivered to the offspring via epigenetic information carrier that coded in sperm. The applicant previously found that a tRNA derived small RNAs-tsRNAs and their modifications could be act as such epigenetic information carrier to transmit paternally high fat diet induced metabolic disorder phenotype to the offspring and a tRNA methyltransferase-Dnmt2 was involved in tsRNA mediated epigenetic inheritance by regulate the m5C modification on tRNAs, in which Dnmt2 deletion abolished the transmitting of paternally acquired metabolic disorder traits to the offspring via sperm RNAs (Science, 2016; Nature Cell Biology, 2018). However, how such epigenetic information coded in sperm under high fat diet? And how Dnmt2 was involved in precisely mediating the formation of such paternal imprinted RNA signature? To further address those unsolved questions, the applicant is going to use the established Dnmt2 deletion mouse model, combined with multiple molecular biology and cell biology methods to work on how tsRNA coded paternal epigenetic information are formed in sperm, in order to further elucidate the underlying mechanism of sperm RNA mediated intergenerational epigenetic inheritance of paternally acquired traits and look forward to provide theoretical basis for guiding eugenics and individualized precision medical treatment in the future.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1186/s12915-023-01537-x
发表时间:2023-02-21
期刊:BMC BIOLOGY
影响因子:5.4
作者:Guo, Huanping;Xia, Lin;Wang, Wei;Xu, Wei;Shen, Xipeng;Wu, Xiao;He, Tong;Jiang, Xuelin;Xu, Yinying;Zhao, Pan;Tan, Dongmei;Zhang, Xi;Zhang, Yunfang
通讯作者:Zhang, Yunfang
DOI:10.3389/fmolb.2022.857875
发表时间:2022
期刊:Frontiers in molecular biosciences
影响因子:5
作者:
通讯作者:
DOI:10.7150/thno.80054
发表时间:2023
期刊:Theranostics
影响因子:12.4
作者:Xia L;Guo H;Wu X;Xu Y;Zhao P;Yan B;Zeng Y;He Y;Chen D;Gale RP;Zhang Y;Zhang X
通讯作者:Zhang X
DOI:10.3389/fmolb.2022.871737
发表时间:2022
期刊:Frontiers in molecular biosciences
影响因子:5
作者:
通讯作者:
DOI:10.1093/molehr/gaac031
发表时间:2022-08-12
期刊:MOLECULAR HUMAN REPRODUCTION
影响因子:4
作者:Guo, Huanping;Shen, Xipeng;Hu, Hua;Zhou, Peng;He, Tong;Xia, Lin;Tan, Dongmei;Zhang, Xi;Zhang, Yunfang
通讯作者:Zhang, Yunfang
精子tsRNA及其RNA修饰调控胚胎表观遗传信息重建介导代际遗传的机制研究
  • 批准号:
    82371727
  • 项目类别:
    面上项目
  • 资助金额:
    49万元
  • 批准年份:
    2023
  • 负责人:
    张云芳
  • 依托单位:
国内基金
海外基金