Transcriptional regulation of domesticated transposable elements-derived promoters in human genome

人类基因组中驯化转座元件衍生启动子的转录调控

• 批准号: 10452608
• 负责人: Bo Zhang
• 金额: $ 37.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10452608
• 关键词: Atlases; Behavior; Big Data; Binding Sites; Bioinformatics; Biological Process; Cells; Code; DNA Transposable Elements; Data; Data Analyses; Development; Elements; Evolution; Genes; Genetic Transcription; Genome; Genomic approach; Genotype-Tissue Expression Project; Human; Human Genome; Mus; Pattern; Phylogenetic Analysis; Play; Proteins; Rodent; Role; Short Interspersed Nucleotide Elements; Surveys; Tissue Differentiation; Tissues; Transcript; Transcriptional Regulation; Trees; Untranslated RNA; cell type; comparative genomics; epigenetic silencing; epigenomics; human tissue; improved; novel; promoter; single-cell RNA sequencing; tool; transcription factor; transcriptome sequencing; Atlases; Behavior; Big Data; Binding Sites; Bioinformatics; Biological Process; Cells; Code; DNA Transposable Elements; Data; Data Analyses; Development; Elements; Evolution; Genes; Genetic Transcription; Genome; Genomic approach; Genotype-Tissue Expression Project; Human; Human Genome; Mus; Pattern; Phylogenetic Analysis; Play; Proteins; Rodent; Role; Short Interspersed Nucleotide Elements; Surveys; Tissue Differentiation; Tissues; Transcript; Transcriptional Regulation; Trees; Untranslated RNA; cell type; comparative genomics; epigenetic silencing; epigenomics; human tissue; improved; novel; promoter; single-cell RNA sequencing; tool; transcription factor; transcriptome sequencing

Project Summary Transposable elements (TEs) comprise roughly half of the human genomes, and some TE subfamilies can even contain hundreds of thousands of copies, such as LINE and SINE elements. Highly enriched transcriptional factor binding sites in the TEs sequence enable TEs the huge regulatory potential to the host genome. Mounting evidence suggests some of TEs escaped from epigenetic silencing and actively involved in multiple biological processes of host genome. TEs are significant contributors to the origin of vertebrate long non-coding RNAs, and some TEs are also found to play roles as promoters in early development and some terminally differentiated tissues. Our recent study found that domesticated rodent-specific TEs can play roles as promoters to initiate the tissue-specific transcription of more than 300 genes during mouse tissue differentiation. However, how the domesticated TEs-derived promoters in the human genome to regulate the gene transcription in distinct tissues and cell types, is not clearly characterized. For example, we do not know how many genes can be transcribed by TEs-derived promoters in particular human tissues; we have no idea about the usage of TEs-derived promoters in the different cell types from the same tissue; finally, how domesticated TEs in the human genome created novel tissue-specific expression pattern of conserved protein- coding genes, is still mystified. Thus, in this proposed project, we will focus on investigating the tissue- and cell type-specific gene transcription controlled by the domesticated TEs-derived promoters in the human genome. Leveraging the big data generated by large consortiums, e.g., ENCODE, Roadmap Epigenomics, GTEx, and Human Cell Atlas, we will perform a systematic survey of the usage of domesticated TEs-derived promoters in the human genome. Firstly, we will identify the TEs that were domesticated as promoters of protein-coding genes and non-coding genes in the human genome, and further characterize the tissue-level expression pattern of domesticated TEs-derived transcripts, by using our established transcripts assemble pipeline to analyze the tissue bulk RNA-seq data generated by ENCODE and GTEx. Secondly, we will investigate the cell-type-specific expression pattern of domesticated TEs-derived transcripts, by reconstructing the single-cell RNA-seq data analysis with novel bioinformatics analysis tool. Finally, we will apply comparative-genomics approaches to create the expression matrix of orthologous TEs-derived protein- coding genes across multi-species, and construct the phylogenetic trees to explore the expression pattern changes of TEs-derived protein-coding genes during evolution.

项目摘要 转座元素（TES）约占人类基因组的一半，而某些TE亚家族则包括 甚至可以包含数十万个副本，例如线条和正弦元素。高度丰富 TES序列中的转录因子结合位点使宿主具有巨大的调节潜力 基因组。越来越多的证据表明，某些TE从表观遗传沉默中逃脱并积极参与 宿主基因组的多个生物学过程。 TE是脊椎动物长的起源的重要贡献者 非编码RNA和一些TE也被发现在早期开发中扮演启动者的角色，有些是 终端分化的组织。我们最近的研究发现，驯养的啮齿动物特异性TE可以扮演角色 作为启动子在小鼠组织期间启动300多个基因的组织特异性转录 分化。但是，如何调节人类基因组中的TES衍生的启动子 不同的组织和细胞类型中的基因转录尚未清楚地表征。例如，我们不知道 TES衍生的启动子在特别的人体组织中可以转录多少基因；我们不知道 关于TES衍生的启动子在同一组织的不同细胞类型中的使用；最后，怎么样 人类基因组中的驯化TE产生了保守蛋白质的新型组织特异性表达模式 编码基因，仍然是神秘的。因此，在这个拟议的项目中，我们将专注于研究组织和组织 细胞类型特异性基因转录由驯养的TES衍生的启动子控制 人基因组。利用大型财团产生的大数据，例如编码，路线图 表观基因组学，GTEX和人类细胞地图集，我们将对驯养的使用系统进行系统的调查 人类基因组中的TES衍生启动子。首先，我们将确定被驯化为 人类基因组中蛋白质编码基因和非编码基因的启动子，并进一步表征 通过使用我们既定的成绩单 组装管道以分析由Encode和GTEX产生的组织大量RNA-seq数据。其次，我们 将研究通过 使用新型的生物信息学分析工具重建单细胞RNA-seq数据分析。最后，我们会的 采用比较基因组学方法来创建直系同源TES衍生蛋白质的表达矩阵 跨多种物种编码基因，并构造系统发育树以探索表达模式 TES衍生的蛋白质编码基因在进化过程中的变化。