Biased eviction of variant histone H3 nucleosomes triggers biofilm growth in Candida albicans

Candida albicans is an opportunistic human pathogen that colonizes the gastrointestinal and genitourinary tracts of healthy individuals. C. albicans yeast cells can switch to filamentous forms. On biotic and abiotic surfaces, the planktonic free-floating yeast cells often form biofilms, a multi-drug-resistant three-dimensional community of yeast and filamentous cells. While alterations in gene expression patterns during planktonic to biofilm growth transitions in C. albicans have been studied, the underlying molecular mechanisms largely remain unexplored. Previously, we identified a histone H3 variant (H3V(CTG)), which acts as a negative regulator of biofilm growth in C. albicans. In the current study, we performed genome-wide profiling of H3V(CTG) nucleosomes in C. albicans planktonic cells and found them to be enriched at promoter regions. In planktonic cells, H3V(CTG)-enriched regions are mostly devoid of histone H3 post-translational modifications that allow active transcription, thus strengthening the role of H3V(CTG) as a negative regulator of biofilm formation. By combining genome-wide transcriptional alterations, nucleosome positioning (MNase-seq), and DNA accessibility (ATAC-seq) assays, we show a significant reduction in the total number of nucleosomes in biofilm cells as compared to planktonic cells indicating a more open chromatin state during biofilm growth. Finally, we propose that H3V(CTG)-nucleosome eviction at promoters of biofilm-relevant genes in biofilm-grown cells contributes to achieve the open chromatin state by facilitating easy promoter access of master regulators (activators and repressors) for modulation of gene expression observed during growth phase transitions.

Automated summary

Candida albicans can switch to filamentous forms and form biofilms, with a significant reduction in nucleosome count and a more open chromatin state in biofilm cells. A histone H3 variant called H3V(CTG) acts as a negative regulator of biofilm growth in Candida albicans.