Project description
Shedding light on the regulation of gene transcription
Evidence produced over the past decade indicates that most of the genome is transcribed, generating various types of RNA molecules. This is known as pervasive transcription and has a documented regulatory role in the transcription of protein-coding genes. The EU-funded uTSSreg project is following an innovative approach to study the regulatory effect of pervasive transcription on promoter activity. Through an in vitro protein depletion strategy in cells, scientists will observe hidden transcriptional events on gene promoters. Results will advance our knowledge on the complex process of protein-coding gene regulation.
Objective
Regulation and fidelity of gene expression is fundamental to the differentiation and maintenance of living organisms. Moreover, understanding how genes are regulated is an essential research question of importance for biomedical application. Although our knowledge about key factors influencing gene expression has increased substantially over the past years, the complexity of gene expression regulation remains elusive. In this project, I intend to discover novel gene expression regulatory circuits operating in mammalian genomes facilitated by pervasive transcription. Although some scattered examples of how pervasive transcription may regulate gene promoter activity exist, no systematic study has been conducted. Here, I will address this question by using a new protein depletion strategy, developed in the host laboratory, to inactivate the nuclear exosome, a major 3’-to-5’ ribonuclease complex, and its co-factors in HeLa and mouse embryonic stem (mES) cells, thus, to create an ideal situation to observe ‘hidden’ cellular transcription events, which would not normally be visible. I intend to assess whether and how this ‘hidden’ transcription contributes to the regulation of promoter activity in HeLa and mES cells, further expanding our knowledge of the regulation of protein-coding genes and ultimately revealing the extent of regulation instigated by pervasive transcription. This study will lay a foundation for future research in the field and at the same time provide novel conceptual information, which might be exploited in prevention or treatment of human diseases.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
8000 Aarhus C
Denmark