The MYST Family Histone Acetyltransferase Sas3 Governs Diverse Biological Processes in Aspergillus fumigatus

The conserved MYST proteins form the largest family of histone acetyltransferases (HATs) that acetylate lysines within the N-terminal tails of histone, enabling active gene transcription. Here, we have investigated the biological and regulatory functions of the MYST family HAT Sas3 in the opportunistic human pathogenic fungus Aspergillus fumigatus using a series of genetic, biochemical, pathogenic, and transcriptomic analyses. The deletion of sas3 results in drastically reduced colony growth, asexual development, spore germination, response to stresses, and the fungal virulence. Genome-wide expression analyses have revealed that the sas3 mutant showed 2,402 significant differentially expressed genes; 1,147 up-regulated and 1,255 down-regulated. The representative up-regulated gene resulting from sas3 is hacA predicted to encode a bZIP transcription factor, whereas the UV-endonuclease UVE-1 was significantly down-regulated by sas3. Furthermore, our Western blot analyses suggest that Sas3 likely catalyzes acetylation of H3K9, K3K14, and H3K29 in A. fumigatus. In conclusion, Sas3 is associated with diverse biological processes and can be a potential target for controlling pathogenic fungi.