Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans

Abstract

Candida albicans is associated with humans, as both a harmless commensal organism and a pathogen. Adaption to human body temperature is extremely important for its growth and morphogenesis. Saccharomyces cerevisiae Esa1, a member of the MYST family HATs (histone acetyltransferases) and the catalytic subunit of the NuA4 complex, and its homologues in other eukaryotes have been shown to be essential for cell growth. To investigate the functional roles of two MYST family HATs, Esa1 and Sas2 in C. albicans, we deleted ESA1 and SAS2 in the C. albicans genome and performed cell growth analyses. Our results demonstrated that C. albicans Esa1 is not essential for general growth but is essential for filamentous growth. The esa1/esa1 mutant cells exhibited sensitivity to thermal, genotoxic, and oxidative stresses but tolerance to cold, osmotic, and cell wall stresses. In contrast, the sas2/sas2 mutant adapted to growth at higher temperatures and promoted filament formation at lower temperatures, resembling the phenotype of a C. albicans strain overexpressing ESA1. Cells with deletions of both ESA1 and SAS2 were inviable, reflecting the functional redundancy in cell growth. C. albicans Esa1 and Sas2 have distinct and synergistic effects on histone acetylation at H4K5, H4K12, and H4K16. Esa1 contributes mainly to acetylation of H4K5 and H4K12, whereas Sas2 contributes to acetylation of H4K16. Our findings suggest that C. albicans Esa1 and Sas2 play opposite roles in cell growth and morphogenesis and contribute coordinately to histone acetylation and gene regulation.

The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

“…Recent studies suggest a pivotal role for chromatin modification and organization in controlling fungal morphogenesis 18 – 20 . Moreover, Efg1 cooperates with the NuA4 histone acetyltransferase (HAT) complex and the ATP dependent chromatin remodeling complex SWI/SNF during hyphal initiation 21 .…”

The Paralogous Histone Deacetylases Rpd3 and Rpd31 Play Opposing Roles in Regulating the White-Opaque Switch in the Fungal Pathogen Candida albicans

“…However, dot1 Δ/Δ strains lacking an H3K79 methylase (26), the sas2 Δ/Δ mutant devoid of a histone acetyltransferase (HAT) (27), and the set2 Δ/Δ methyltransferase mutant (28) showed increased O cell formation. Conversely, elp3 Δ/Δ mutants lacking a putative HAT (29) and the hos1 Δ/Δ mutant lacking an HDAC (20) displayed significantly decreased W/O switching.…”

Chromatin Structure and Drug Resistance in Candida spp.

“…The sensitivity of Y-H transition to histone acetylation is also evident in mutant strains with compromised KAT functionality. In C. albicans strains lacking a subunit of the NuA4 KAT complex (Ca_yng2Δ/Δ ), or those containing the mutation Ca_esa1 Δ/Δ, hyphal development on both solid and liquid media is severely affected [ 113 , 114 ]. Similarly, loss of function of the Ca_Ada2p, which makes up part of the SAGA KAT complex renders C. albicans unable to produce hyphal filaments in vitro, and interestingly, also in vivo in a Caenorhabditis.…”