Final Report Summary - TISSUECONTROLNETWORK (Genetic interaction networks in a self-renewing human tissue)
Both epigenetic factors, microRNAs and DNA binding factors have the potential to control transcript levels of large sets of genes through transcriptional and post-transcriptional mechanisms. However, how these factors cooperate to regulate biological processes is poorly understood. This project aims to pioneer the concept of genetic interactions between coding (chromatin-factors), DNA binding factors and non-coding RNAs (miRNAs) using primary human epidermal stem cells as a well-characterised and clinically relevant model system. My lab has silenced all individual miRNAs expressed as well as 145 transcription factors in these cells to measure their contribution to stem cell renewal and differentiation. An innovative Bayesian statistical framework will be employed to predict which DNA binding factors and chromatin- factors function together these conditions. Understanding which genes in the genome cooperate, and how they do so, will not only deepen our understanding of normal biology, it will also help rationalise targeted (combination) therapies for disease, a major goal in modern clinical medicine.