多组学大数据整合分析揭示早期胚胎发育过程中基因表达调控信息的变化规律  

Integrative Multi-omics Analysis of Gene Regulation Mechanism during Early Embryonic Development

作　　者：江琦 汤小晗[2] 陶欢 王军婷 白雪梅 李昊 卢美松[2] JIANG Qi;TANGXiao-han;TAO Huan;WANG Jun-ting;BAIXue-mei;LI Hao;LU Mei-song(Tong fang Co.,Ltd.Beijing,100083,China;The First Clinical Hospital affiliated to Harbin Medical University,Harbin,Heilongjiang,150081,China;Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing,100850,China)

机构地区：[1]同方股份有限公司,北京100083 [2]哈尔滨医科大学附属第一医院,黑龙江哈尔滨150081 [3]军事科学院军事医学研究院辐射医学研究所,北京100850

出　　处：《现代生物医学进展》2021年第12期2241-2244,共4页Progress in Modern Biomedicine

基　　金：北京市自然科学基金项目(5204040)。

摘　　要：目的:探究哺乳动物早期胚胎发育过程中基因表达调控信息的变化规律。方法:收集小鼠早期胚胎发育各时期的RNA-seq,ATAC-seq,MethylC-Seq和H3K4me3 ChIP-seq数据进行整合分析,观察小鼠早期胚胎发育各时期转录因子表达量的变化,计算各时期基因表达量与转录因子结合位点数量及染色质可及性的相关性,筛选各时期表达量前10%的基因,统计其表达量和转录因子占比,并进行启动子可及性分析。根据前期报道的转录因子三节点调控网络,对早期胚胎各时期转录因子调控网络的富集模式进行分析。根据多组学数据分析结果,推测早期胚胎发育调控过程中转录因子和表观遗传修饰信息的共调控模型。结果:转录因子数量和调控关系变化以及染色质可及性、DNA甲基化修饰、组蛋白修饰等表观遗传修饰共同调控早期胚胎发育各时期的基因表达,这些因素在不同时期发挥不同程度的调控作用。结论:转录因子和表观遗传修饰在早期胚胎发育过程中动态调控基因表达。Objective:Exploration of gene regulation mechanism during early mammalian embryonic development.Methods:RNA-seq,ATAC-seq,MethylC-Seq and H3K4me3 ChIP-seq data of mouse early embryonic development were collected for integrative analysis.Expression change of transcription factors during mouse early embryonic development were counted.Correlation between gene expression and number of transcription factor binding sites and chromatin accessibility were calculated.Highly expressed(top 10%)genes in different stages of early embryonic development were filtered in which proportion of transcription factors and chromatin accessibility in promoter regions were calculated.According to three-node regulatory network of transcription factors reported previously,the enrichment mode of transcription factors regulatory network in different stages of early embryonic development were analyzed.Besides,co-regulation model of transcription factors and epigenetic modification of early embryonic development was simulated based on integrative analysis of multi-omics data.Results:Number and regulatory mode of transcription factors and epigenetic modification,such as chromatin accessibility,DNA methylation,histone modification,co-regulate gene expression during early embryonic development.These factors show different regulatory mode in different stages of early embryonic development.Conclusions:Transcription factors and epigenetic modification play highly dynamic regulatory roles in gene expression during early embryonic development.

关 键 词：多组学整合分析 早期胚胎发育 转录因子 表观遗传修饰 基因表达调控 

分 类 号：R-33[医药卫生] Q132.7[生物学—普通生物学]