Analysis of the relationship between the genome architecture and its functioning is a priority research field in molecular genetics. The formation of independent transcriptional domains and spatial contacts between regulatory regions of individual loci or between chromosomes depend on architectural proteins. We study the mechanisms allowing the Drosophila architectural protein Su(Hw) to form complexes that have different regulatory activities, specifically bind to genomic sites, and provide for long-distance interactions between enhancers and promoters.
The Su(Hw)-dependent protein complex is a unique model, since its basic structural components having an effect on its activity are already known. These are the Su(Hw), Mod(mdg4), and CP190 proteins. It is known that the Mod(mdg4)-67.2 isoform interacts only with the Su(Hw) protein. However, the mod(mdg4) locus encodes more than 30 protein isoforms with different C-terminal domains. The role of other Mod(mdg4) isoforms in transcription regulation and organization of chromatic structure remains obscure. We assume that Mod(mdg4) isoforms may facilitate site-specific binding of transcription-regulating protein complexes. Therefore, we are studying the mechanism of interaction between different Mod(mdg4) isoforms and DNA-binding proteins.
In our work we combine the methods of classical genetics (crossing of Drosophila mutants with subsequent genetic and phenotypic analysis of the offspring) with modern methods of molecular biology (CRISPR / Cas9 genome editing, qChIP analysis, RT-PCR, GST Pull Down, etc.).