Epidermal Gene Regulation by Transcription Elongation and Termination

项目摘要 这个项目的长期目标是阐明基本的基因调控机制。 表皮组织动态平衡。数以千计的基因在未分化的和未分化的 分化的角质形成细胞，但我们目前对基因调控机制的理解仍然 不完整。在转录的背景下，这是基因表达的第一个也是关键的阶段，许多努力 已经集中在转录起始的第一步。另外两个转录步骤的作用， 即延伸和终止步骤，在很大程度上仍未被探索。因此，这项研究计划是 旨在通过表征转录延伸和转录的调节作用来弥合这一知识鸿沟 控制表皮基因表达的终止过程。 我们的初步特征表明，未分化和分化的角质形成细胞获得 转录延伸和终止调节因子的差异表达模式。利用我们的专业知识 在基因组学、蛋白质组学和人类组织模型上，我们将确定转录延伸和 终止调节因子与它们相互作用的蛋白协同作用，以差异调节伸长和 终止过程以控制表皮祖细胞的维持与终末组织分化。 表皮基因表达失调是人类皮肤谱系发病的基础 包括牛皮癣、慢性伤口愈合和癌症在内的疾病。增加对基因调控的理解 由这些特征不足的延长和终止过程控制可以产生新的治疗方法 治疗人类皮肤病的想法。

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.