Veneta Gerganova

• A lot of vital postulations were made at the dawn of genetics, even before the elucidation of the DNA structure – what is a gene, where is it located within the cell, how is it used as an information carrier? Nowadays, the questions have become exponentially more complex and understanding the mechanisms of genetic regulation is at hand. The road that scientific advancement took, specifically the early comprehension of proteins as a driving force of biological processes, left a mark on the study of genetics. It aided the identification of a plethora of DNA-binding proteins and elucidated their involvement in the replication, transcription and organisation of the molecule. In parallel, further research partially revealed the internal organization of the DNA and we gained knowledge of the genetic code of a remarkable number of organisms via sequencing entire genomes. All this information, however, should be coupled to another property of the DNA – its structure. Studies on DNA architecture revealed the existence of higher order structures that exert global control of transcriptional activity through variations of DNA topology, or the analogue mode of regulation. Here I address the importance of gene position in the bacterial chromosome by carrying out the first systematic gene relocation study in which I show that the relocation of a gene encoding for the abundant regulatory protein FIS leads to global changes in the bacterial phenotype. In order to make a fair assessment of those global positioning effects, I first carried out an in-depth investigation of the local regulation of the fis promoter region, which unveiled that RNA polymerase can serve as an architectural factor modulating the activity of transcription initiation complexes in an enhancer-like fashion. These two observations, regarding the global gene order and the complex local interactions are a step towards implementing a holistic methodology into the study of the DNA organization and dynamics.