Mcm2调控亲本组蛋白表观遗传信息传递的分子机制和功能研究
批准号:
32001043
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
孙亚萍
依托单位:
学科分类:
生命组学技术
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
孙亚萍
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中文摘要
生物遗传除了依赖DNA序列外,组蛋白及其修饰所携带的表观遗传信息,即组蛋白密码,也是调控染色质结构及基因表达的重要机制。因此,对组蛋白密码遗传方式的揭示,将对深入了解基因转录调控机制及细胞分裂、分化调控机理有着重要的意义。2018年亲本组蛋白被发现是近乎均匀对称的分配到DNA复制的前导链和后随链,Mcm2是调控这一过程的重要分子,但Mcm2调控亲本组蛋白分配的分子机制及其对细胞命运决定的影响尚未阐明。因此,本课题拟以小鼠胚胎干细胞为研究对象,利用基于TurboID临近标记的蛋白质组学技术,结合eSPAN技术鉴定并筛选协同Mcm2调控组蛋白分配的潜在蛋白分子,另外一方面,也将进一步明确Mcm2调控亲本组蛋白分配对干细胞分化功能的影响。本项目的研究将阐明Mcm2调控亲本组蛋白表观修饰遗传的分子机制及其对干细胞命运决定的影响,为干细胞的临床应用提供理论指导。
英文摘要
In addition to the DNA sequence, the epigenetic information carried by histones and their modifications, namely the histone code, is also important mechanisms for regulating chromatin structure and gene expression. Therefore, the inheritance method of the histone code will be of great significance for understanding the mechanism of gene transcription regulation and the mechanism of cell division and differentiation. In 2018, the parent histones were found to be almost symmetrically distributed to the leading and lagging strands of DNA replication. Mcm2 is an important molecule that regulates this process, but the molecular mechanism of Mcm2-regulated parent histone distribution and its effect on cell fate has not yet been clarified. Therefore, this project intends to take mouse embryonic stem cells as the research object, and use TurboID-based proteomic technology, combined with eSPAN technology to identify and screen potential protein molecules that cooperate with Mcm2 to regulate histone distribution. On the other hand, the effect of Mcm2- regulated parental histone distribution on stem cell differentiation is also further clarified. The research of this project is helpful to clarify the molecular mechanism of Mcm2 regulating the distribution of parental histones and its effect on stem cell fate, and provide theoretical guidance for the clinical application of stem cells.
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DOI:10.3389/fmicb.2023.1267196
发表时间:2023
期刊:Frontiers in microbiology
影响因子:5.2
作者:
通讯作者:
DOI:10.1038/s41588-023-01477-w
发表时间:2023-09
期刊:Nature Genetics
影响因子:30.8
作者:Qing Wen;Jiaqi Zhou;Congcong Tian;Xinran Li;G. Song;Yuan Gao;Yaping Sun;Chiyuan Ma;Sitong Yao;Xiaoyan Liang;Xing Kang;Nan Wang;Yuan Yao;Hongbao Wang;Xiaohuan Liang;Jialin Tang;S. Offer;Xiaohua Lei;Chuanhe Yu;Xiangyu Liu;Zichuan Liu;Zhiquan Wang;Haiyun Gan
通讯作者:Qing Wen;Jiaqi Zhou;Congcong Tian;Xinran Li;G. Song;Yuan Gao;Yaping Sun;Chiyuan Ma;Sitong Yao;Xiaoyan Liang;Xing Kang;Nan Wang;Yuan Yao;Hongbao Wang;Xiaohuan Liang;Jialin Tang;S. Offer;Xiaohua Lei;Chuanhe Yu;Xiangyu Liu;Zichuan Liu;Zhiquan Wang;Haiyun Gan
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