Epidermal Gene Regulation by Transcription Elongation and Termination

通过转录延伸和终止调节表皮基因

基本信息

批准号：
10460273
负责人：
Xiaomin Bao
金额：
$ 34.62万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10460273
关键词：
Basal cell carcinoma Binding C-terminal CRISPR interference Candidate Disease Gene Cells ChIP-seq Chimeric Proteins Cleavage And Polyadenylation Specificity Factor Co-Immunoprecipitations Complex Coupled DNA Polymerase II Data Set Development Differentiated Gene Differentiation and Growth Disease Epidermis Epithelial Equilibrium Future Gene Expression Gene Expression Regulation Genes Genetic Transcription Genomic Segment Genomics Global Change Goals Homeostasis Human Impairment Individual Knowledge Maintenance Malignant Neoplasms Mass Spectrum Analysis Monitor Natural regeneration Pathogenesis Pattern Phosphorylation Play Poly A Polyadenylation Positive Transcriptional Elongation Factor B Process Proteins Proteomics Psoriasis RNA RNA Interference Regulator Genes Research Role Serine Signal Transduction Site Squamous cell carcinoma Testing Tissue Differentiation Tissue Model Tissues Transcription Elongation Transcription Initiation Transcription Repressor Transcriptional Elongation Factors Undifferentiated Work chronic wound design differential expression dosage epidermal stem cell gene function gene product human disease human tissue inhibitor insight keratinocyte keratinocyte differentiation knock-down novel novel therapeutics premature recruit scaffold skin disorder tissue regeneration transcription termination transcriptome sequencing wound healing

项目摘要

Project Summary The long-term goal of this project is to elucidate the fundamental gene regulatory mechanisms controlling epidermal tissue homeostasis. Thousands of genes are differentially expressed between undifferentiated and differentiated keratinocytes, yet our current understanding of the gene regulatory mechanisms still remain incomplete. In the context of transcription, which is the first and crucial stage of gene expression, a lot of efforts have been concentrated on the first transcription initiation step. The roles of two other transcription steps, namely the elongation and termination steps, remain largely unexplored. Therefore, this research plan is designed to bridge this knowledge gap by characterizing the regulatory roles of transcription elongation and termination processes in controlling epidermal gene expression. Our preliminary characterization revealed that undifferentiated and differentiated keratinocytes acquire differential expression patterns of transcription elongation and termination regulators. Leveraging our expertise on genomics, proteomics, and human tissue models, we will determine how transcription elongation and termination regulators cooperate with their interacting proteins to differentially regulate the elongation and termination processes to control epidermal progenitor maintenance versus terminal tissue differentiation. Dysregulation of epidermal gene expression underlies the pathogenesis of a spectrum of human skin diseases including psoriasis, chronic wound healing, and cancer. Increased understanding of gene regulation controlled by these under-characterized elongation and termination processes can generate novel therapeutic ideas for treating human skin diseases.

项目摘要该项目的长期目标是阐明控制基因调节机制表皮组织稳态。在未分化和分化的角质形成细胞，但是我们目前对基因调节机制的理解仍然存在不完整。在转录的背景下，这是基因表达的第一个至关重要的阶段，很多努力已经集中在第一个转录启动步骤上。其他两个转录步骤的作用，即伸长和终止步骤，在很大程度上尚未探索。因此，该研究计划是旨在通过表征转录伸长的调节作用和控制表皮基因表达的终止过程。我们的初步表征表明，未分化和分化的角质形成细胞获得转录伸长和终止调节剂的差异表达模式。利用我们的专业知识关于基因组学，蛋白质组学和人体组织模型，我们将确定转录伸长和终止调节器与其相互作用的蛋白质合作，以差异调节伸长率和控制表皮祖细胞维持与终末组织分化的终止过程。表皮基因表达的失调是人类皮肤谱的发病机理的基础包括牛皮癣，慢性伤口愈合和癌症在内的疾病。对基因调节的了解增加由这些特征不足的伸长率和终止过程控制可以产生新颖的治疗性治疗人皮肤疾病的想法。