In slide at top of page:
Models for how INO80-C and Cohesin regulate HSP Gene Expression and 3D-Genome Repositioning in response to acute thermal stress.
Vickky Pandit, PhD
BS, Pharmacy, Poona College of Pharmacy, 2012
MS, Pharmacology, Nottingham Trent University. 2014
PhD, Biochemistry & Molecular Biology, LSUHS, 2023
All cell types within an organism possess the same genes distributed in a nearly random fashion along each of that organism’s chromosomes. In multicellular organisms, the uniqueness of a cell (its identity) is conferred by cell type-specific gene expression that occurs during differentiation and development. The eukaryotic genome is compacted into chromatin with the help of proteins called histones that form octamers (two each of H2A, H2B, H3 & H4). Each histone octamer coils DNA into two superhelical turns (=nucleosome) that gives a defining architecture to chromatin. Not surprisingly, chromatin structural dynamics play a crucial role in the regulation of gene expression in all eukaryotes.
Chromatin Remodelling Complexes (CRCs) are modular proteins that alter chromatin architecture by repositioning, ejecting or changing the composition of histone octamers, giving transcription machineries access (or restricting it) to regulatory DNA elements, thus ultimately regulating gene expression. Mutations in the genes encoding chromatin remodelling complexes have been found to be associated with several human disorders, including cancer.
Recent studies have suggested that eukaryotic cells control transcription by formation of phase-separated, multi-molecular assemblies. For example, super-enhancers inside the nucleus of a mouse embryonic stem cell appear to phase-separate from the nucleoplasm. Along similar lines, the Gross lab has shown that Heat Shock Protein (HSP) genes in the model eukaryote Saccharomyces cerevisiae (budding yeast) ‘coalesce’ upon their transcriptional activation into distinct intranuclear foci. The goal of my project is to investigate the role of ATP-dependent chromatin remodelling complexes (such as Swi/Snf, RSC, ISWI, CHD, INO80) in orchestrating the 3D topology of transcriptionally active genes, particularly HSP genes whose transcription is under the regulation of Heat Shock Factor 1 (Hsf1). I will also investigate the potential role of CRCs in the formation of multi-molecular, phase-separated assemblies that are observed upon HSP gene activation.