Transcriptional loops meet chromatin: a dual-layer network controls white-opaque switching in Candida albicans.
The human pathogen Candida albicans is able to undergo a reversible switch between two distinct cell types called white and opaque, which are considered different transcriptional states of cells harbouring identical genomes. The present model of switching regulation includes the bistable expression of a master switch gene that is controlled by multiple transcriptional feedback loops. Here, we show that chromatin-modifying enzymes constitute an additional important regulatory layer of morphogenetic switching. We identify eight chromatin modifiers as switching modulators. Extensive epistasis analysis maps them into at least two independent signalling pathways overlaying the known transcriptional network. Interestingly, we identify the conserved Set3/Hos2 histone deacetylase complex as a key regulator relying on the methylation status of histone H3 lysine 4 for switching modulation. Furthermore, we demonstrate that opaque to white switching is facilitated by the presence of adenine in vitro, but adenine has no effect on switching once the Set3/Hos2 complex is disrupted. Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans.
Hnisz
Denes
D
Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter, A-1030 Vienna, Austria.
Schwarzmüller
Tobias
T
Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter, A-1030 Vienna, Austria.
Kuchler
Karl
K
Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter, A-1030 Vienna, Austria.
D000225:Adenine / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005812:Genes, Switch; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D012331:RNA, Fungal / Q000235:genetics; D014158:Transcription, Genetic
D002843:Chromatin; D005656:Fungal Proteins; D006657:Histones; D012331:RNA, Fungal; D006655:Histone Deacetylases; D000225:Adenine