Exploring chromatin functions in yeast spores – EpiSpores

SCIENTIFIC CONTEXT. Unicellular organisms need to adapt to rapid and unanticipated changes in their environment. Spores ensure their survival by encapsulating the genome in a protective configuration while awaiting optimal growth conditions. Indeed, yeast spores enter into a quiescent state with minimal metabolic activity and are surrounded by a thick protective wall. Yet, protecting the integrity of the genome in these conditions involves not only a dramatic decrease in transcriptional activity, an extreme nuclear compaction, but also the capacity to completely revert these processes to allow germination. The mechanisms involved in the establishment of genomic quiescence in spores, the protection of their genome and its reactivation, remain unknown.

OBJECTIVE. Several lines of evidence show that chromatin is highly compacted in spores. In addition, histone H4 is hyperacetylated and this modification is essential for spore viability. This observation seems counter-intuitive because H4 acetylation (H4ac) is usually associated with transcription activation and open chromatin. Therefore, the general objectives of this project are to understand (i) the mechanisms by which H4 is hyperacetylated in spores, (ii) how H4ac is compatible with quiescence in spores and their chromatin compaction, (iii) whether and how H4ac prepares genome reactivation observed during early germination.

IMPACT. Through EpiSpores, we will improve our general knowledge on H4ac signalling pathways, chromatin organisation and transcription regulation. Furthermore, yeast spores provide an alternative model system to investigate the molecular mechanisms of quiescence entry, maintenance and exit in all eukaryotic cells. Finally, our previous work on yeast spores has been translated to the treatment of fungal infections, collectively responsible for 1.5 millions of deaths per year. Our future work exploring chromatin signalling pathways in Candida albicans and their functional role in the virulence of this pathogenic yeast will be based on the technological development of this proposal.

CONSORTIUM. This project brings together young researchers, by academic standards, with collective and synergetic expertise in yeast biology, genetics, biochemistry, interactomics, high-throughput genetics, super-resolution microscopy and epigenomic approaches.