Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Hyphal development in Candida albicans requires two
temporally linked changes in promoter chromatin for
initiation and maintenance
Yang Lu, Chang Su, Allen Wang and Haoping Liu
Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
Phenotypic plasticity is common in development. For Candida albicans, the most
common cause of invasive fungal infections in humans, morphological plasticity is
its defining feature and is critical for its pathogenesis. Unlike other fungal pathogens
that exist primarily in either yeast or hyphal forms, C. albicans is able to switch
reversibly between yeast and hyphal growth forms in response to environmental
cues. Although many regulators have been found involved in hyphal development,
the mechanisms of regulating hyphal development and plasticity of dimorphism
remain unclear. Here we show that hyphal development involves two sequential
regulations of the promoter chromatin of hypha-specific genes. Initiation requires a
rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal
morphogenesis via activation of the cAMP-PKA pathway. Maintenance requires
promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of
rapamycin) signalling. Hda1 deacetylates a subunit of the NuA4 histone
acetyltransferase module, leading to eviction of the NuA4 acetyltransferase module
and blockage of Nrg1 access to promoters of hypha-specific genes. Promoter
recruitment of Hda1 for hyphal maintenance happens only during the period when
Nrg1 is gone. The sequential regulation of hyphal development by the activation of
the cAMP-PKA pathway and reduced Tor1 signalling provides a molecular
mechanism for plasticity of dimorphism and how C. albicans adapts to the varied
host environments in pathogenesis. Such temporally linked regulation of promoter
chromatin by different signalling pathways provides a unique mechanism for
integrating multiple signals during development and cell fate specification.
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