Hierarchical layers of gene control in the innate response to infection


Infection causes drastic shifts in gene expression towards antimicrobial gene signatures. We will examine the transcriptional response of bone marrow macrophages to infection with the intracellular bacterium Listeria monocytogenes (Lm), focusing on changes to diagnostic chromatin modifications, DNA accessibility and intra- as well as interchromosomal interactions. We will concentrate on STAT-dependent type I interferon (IFN-I)-induced genes (ISG) and a group of ‘synergy genes’, whose promoter activation requires cooperative activity of the IFN-I/STAT and NFkappaB pathways. ISG and synergy genes represent distinct regulatory entities and we shall examine their chromatin landscapes for differences before and following infection.

Our major goal is to derive a comprehensive view of how STATs determine genome structure and chromatin landscapes and thereby coordinating gene transcription during microbial infection.

Within the project we aim to determine how diverse regulatory input to ISG and synergy genes derives from different chromosomal topologically associated domains (TAD). Genome editing will be used to validate the functional relevance of enhancers that regulate ISG and synergy genes.


Max F. Perutz Laboratories

University Vienna
Dr. Bohr-Gasse 9
1030 Vienna