EUROCORES_EURODYNA 1. Call_Control of Stress- and Interferon regulated Gene Expression by Transcription Factors, Histone Modification and Nuclear Compartmentalisation

The precise regulation of gene expression in response to extracellular stimuli plays a key role in life and biological diversity. Specific transcription factors, general transcription machinery, histone modifying enzymes, chromatin remodeling complexes, as well as nuclear architecture all have roles in gene transcription. How these individual events are coordinated in time and space, and integrated into appropriate transcriptional responses is a challenging yet unresolved question. We will address this issue using as a model the transcription of stress and interferon regulated genes. Both signalling pathways can be activated by independent stimuli and may therefore be studied separately. However, under physiological conditions, the stress and interferon signalling cascades are often activated simultaneously resulting in enhanced transcriptional responses. This synergism is essential for defense against pathogens and in tumor surveillance. Our studies on the order, location and contribution of stress and interferon-induced changes in chromatin modification and nuclear architecture will improve our understanding of the regulation of gene expression and open up new possibilities to combat diseases, such as cancer and infections. The availability of cells and animals with specific genes of the stress and interferon pathways inactivated will enable us to test the working hypotheses under physiological conditions.