dr. Remus Dame: Fine-tuning the structural organization of prokaryotic genomes

Abstract

Loop formation is key to the global organization of genomes in organisms from all three domains of life. Genomes are organized dynamically and their re-modelling is implied in translating external signals into transcription of specific genes. The bacterial chromatin protein H-NS and the archaeal chromatin protein Alba are capable of forming bridges between DNA segments in vitro and thus candidates for genomic loop formation in vivo. H-NS is a global regulator of transcription and a similar role has been suggested for Alba. We investigate how the DNA bridging activity of these proteins is fine-tuned by physico-chemical conditions and interaction with other proteins. We use a multi-disciplinary approach to address this question in vitro and in vivo, employing tools from biophysics, biochemistry, chemical biology and genetics. We demonstrate that for both proteins there is a delicate balance between two binding modes (stiffening and bridging), which can be shifted when conditions are changed or interaction partners are present. Our observations yield models for fine-tuning of genome organization and for the translation of changes in genome organization into transcriptional activity.