Epigenetics and genome stability in the human fungal pathogen Candida albicans

Large blocks of DNA repeats are commonly assembled into heterochromatin. Heterochromatic regions impose a transcriptionally repressive environment that can propagate over long distances stochastically silencing native genes as well as reporter genes inserted at these regions independently of DNA sequence. Heterochromatin, associated with repressive histone marks, not only down-regulates transcription but also inhibits recombination at repetitive elements. This epigenetic regulation could be a key regulatory step in organisms, such as microbial pathogens, that have to adapt rapidly to different environments. Here for the first time, we analysed the chromatin state of C. albicans repetitive elements and addressed whether and how this epigenetic state controls C. albicans genome stability. The results show that classic SIR2-dependent heterochromatin is assembled at the rDNA and telomeres. Interestingly, heterochromatin at telomeres is plastic and remodelled upon environmental changes. Pericentromeric regions and MRS (Mayor Repeated Sequences) are assembled into permissive chromatin bearing features of both heterochromatin and euchromatin. Surprisingly, SIR2-dependent heterochromatin does not control recombination at the rDNA. However, it inhibits recombination at the TRE (TLO Recombination Element) sequence associated with some TLO genes at subtelomeric regions. These results show that epigenetic factors promote differential genome stabitlity at different loci.