Epidermal Gene Regulation by Transcription Elongation and Termination

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.

Grant Number: 5R01AR075015-05
NIH Institute/Center: NIH
Principal Investigator: Xiaomin Bao