Tracing the Evolutionary Transition of Nucleosome Assembly

• Applicant: Professorin Dr. Sandra Brigitte Hake
• Subject Area: General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468544632

Non-allelic isoforms of canonical histones, known as histone variants, play important roles in indexing a genome into multiple epigenomes. Incorporation of histone variants and associated factors at specific genomic loci play vital roles in lineage-specific gene expression in multicellular organisms. Based on their presence across the genome, specific histone variants are associated with gene activation or gene silencing. Histones and their variants are loaded into nucleosomes to form chromatin in a replication-dependent (RD) or replication-independent (RI) manner by specific chaperone complexes. Most unicellular eukaryotes, including the budding yeast Saccharomyces cerevisiae or the fission yeast Schizosaccharomyces pombe, have only one form of the histone H3 protein. However, the same histone H3 protein can be loaded preferentially in a RD or RI manner by specific histone chaperone complexes. On the other hand, humans and other multicellular eukaryotes have many variants of histone H3 that are loaded in a RD or RI manner by several dedicated evolutionarily conserved (both functionally and structurally) histone chaperone complexes. Hence, it remains unknown whether histone variants and their loading into nucleosomes by specific chaperone complexes have co-evolved, or whether the evolutionary appearance of a histone variant is independent of specific chaperone complexes. Candida albicans is one of the most frequently isolated fungal pathogens from immunocompromised patients and the primary cause of nosocomial infections worldwide. The unique appearance of a histone H3 variant (H3VCTG) in this unicellular eukaryote and its dynamicity in modulating morphogenetic transitions has demonstrated its importance in regulating planktonic to biofilm growth transition. However, there exists a gap in our understanding of the molecular mechanism by which H3VCTG regulates gene expression. This project proposal aims to identify the roles of evolutionarily conserved chaperone complexes, known and unknown assembly and disassembly factors associated with H3VCTG, as it gets loaded to form nucleosomes. These studies will lead to the identification of variant specific chaperones, the functional conservation and diversification of known chromatin-associated proteins as well as novel factors assisting H3VCTG in its biofilm function. Subsequently, to shed light on the evolution of chaperone-dependency of this unusual variant, we plan to express H3VCTG in heterologous systems: unicellular budding yeast and multicellular humans. This will aid in tracing the functional drift in chaperone and their histone recognition principle across the evolutionary time scale.

• DFG Programme: Research Grants
• International Connection: India
• Partner Organisation: Department of Biotechnology (DBT) ; Ministry of Science and Technology
• Cooperation Partner: Professor Dr. Kaustuv Sanyal