母源性转录因子Otx2的磷酸化对胚胎基因组激活的影响

批准号:
32000564
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
张天镭
依托单位:
学科分类:
早期胚胎发育及细胞谱系建立
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
张天镭
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中文摘要
哺乳动物早期胚胎的发育由卵子积累的母源性因子调控,随着胚胎基因的转录表达,胚胎从母源型调控向合子型调控转变。目前关于母源性因子是如何触发胚胎基因组激活(EGA)是发育生物学中一个长期存在较多争议的问题。本项目组基于少量细胞的LiCAT-Seq方法系统绘制了染色质的可及性和转录基因的图谱,多组学分析发现母源性转录因子Otx2基因在早期胚胎中的表达量极高且结合染色质的开放位点最多,具有调控EGA的巨大潜能;并通过Trim-away技术证实Otx2参与了EGA的激活和胚胎发育。同时发现Otx2在卵母细胞和受精卵中处于未激活状态定位于细胞质中,直到2-Cell时期才被活化入核。因此本研究计划从体外水平和体内水平验证Otx2对EGA的调控,解析Otx2调控EGA过程中对染色质重构的影响;并鉴定出早期胚胎中活化Otx2的磷酸化激激酶。本研究将为深入了解母源性转录因子在胚胎发育中作用提供新的视角。
英文摘要
The initially embryogenesis is regulated by the maternal factors from oocyte in mammals. Embryonic transcription begins during the maternal to zygotic transfer of control during embronic gene activation (EGA). How maternal factors trigger embryonic genome activation (EGA) has long been a controversial puzzle. Based on the liCAT-Seq (low-input chromatin accessibility (CA) and transcriptome sequencing), our group mapped the chromatin accessibility and transcriptome landscapes for human preimplantation embryos. We have found that the maternal transcription factor Otx2 gene had the great potential to regulate EGA with high expression in the early embryo. Besise, Otx2 was confirmed to be involved in EGA and embryonic development by Trim-away technique. At the same time, Otx2 was found to be inactive in oocytes and zygotes for located in the cytoplasm, until the 2-cell embryo period. Therefore, this study aims to verify the regulation of Otx2 on EGA in vitro and in vivo to analyze the role of Otx2 on chromatin remodeling during the regulation of EGA and identify the phosphorylated kinases which work for Otx2. Our research will provide a new perspective for further understanding of the role of maternal transcription factors in embryonic development.
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DOI:10.1093/molehr/gaac028
发表时间:2022-07-29
期刊:MOLECULAR HUMAN REPRODUCTION
影响因子:4
作者:Dai, Jing;Chen, Yongzhe;Lin, Ge
通讯作者:Lin, Ge
DOI:10.1016/j.isci.2023.106158
发表时间:2023-03-17
期刊:ISCIENCE
影响因子:5.8
作者:Zhang, Xiaoru;Zhang, Changquan;Zhou, Di;Zhang, Tianlei;Chen, Xueqin;Ren, Jinlin;He, Caixia;Meng, Fei;Zhou, Qinwei;Yang, Qiaohui;Dai, Congling;Lin, Ge;Zeng, Sicong;Leng, Lizhi
通讯作者:Leng, Lizhi
DOI:10.1016/j.ajhg.2021.02.004
发表时间:2021-03-04
期刊:AMERICAN JOURNAL OF HUMAN GENETICS
影响因子:9.8
作者:Dai, Jing;Zhang, Tianlei;Lin, Ge
通讯作者:Lin, Ge
探究母源性转录因子 Otx2 参与人类胚胎基因组的激活(EGA)的分子机制
- 批准号:2021JJ40348
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2021
- 负责人:张天镭
- 依托单位:
国内基金
海外基金
