Abstract
Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli. Strikingly, HIR1-deficient cells display altered transcriptional amplitudes upon hyphal initiation, suggesting that Hir1 affects transcription by establishing transcriptional thresholds required for driving morphogenetic cell-fate decisions. Furthermore, ectopic expression of the transcription factor Ume6, which facilitates hyphal maintenance, rescues filamentation defects of hir1Δ/Δ cells, suggesting that Hir1 impacts the early phase of hyphal initiation. Hence, chromatin chaperone-mediated fine-tuning of transcription is crucial for driving morphogenetic conversions in the fungal pathogen C. albicans.
Highlights
Chromatin plays fundamental roles in gene regulation during most cellular differentiation processes
We reasoned that a functional connection may exist between hyphal formation and chromatin assembly mediated by the HIR histone chaperone complex
We demonstrate a genetic link between replication-independent chromatin assembly and the transcriptional control of morphogenesis in the human fungal pathogen C. albicans
Summary
Chromatin plays fundamental roles in gene regulation during most cellular differentiation processes. Chromatin architecture and functions have been conserved from human embryonic development to morphogenetic cell fate decisions in unicellular eukaryotes including the fungal pathogen Candida albicans[1,2,3]. The functional status of chromatin as well as its architecture can be altered by chromatin modifications including chromatin remodeling through the concomitant assembly and disassembly of nucleosomes This process is guarded and facilitated by conserved histone chaperones acting in replication-dependent and –independent pathways[23]. Asf[1] shuttles modified H3/ H4 dimers into the nucleus to a panel of other histone chaperones for chromatin assembly coupled to DNA replication, DNA damage repair, heterochromatin maintenance or transcription[24, 27]. Hir[1] might affect the fine-tuning of transcriptional responses by regulating local chromatin architecture in target genes, thereby altering affinities of dedicated transcriptional regulators to cognate cis-acting sites, as well as the decoration by and displacement of transcriptional co-factors and modulators
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