4.5 Article

Negative regulation of biofilm development by the CUG-Ser1 clade-specific histone H3 variant is dependent on the canonical histone chaperone CAF-1 complex in Candida albicans

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MOLECULAR MICROBIOLOGY
卷 -, 期 -, 页码 -

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WILEY
DOI: 10.1111/mmi.15050

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chromatin; filamentation; H3V(CTG); HIR; hyphae

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The CUG-Ser1 clade-specific histone H3 variant (H3V(CTG)) is a negative regulator of planktonic to biofilm growth transition in Candida albicans. The CAF-1 chaperone complex, specifically the Cac1 and Cac2 subunits, is involved in loading H3V(CTG) and its absence leads to increased filamentation and robust biofilm formation. The HIRA chaperone complex does not play a significant role in biofilm growth.
The CUG-Ser1 clade-specific histone H3 variant (H3V(CTG)) has been reported to be a negative regulator of planktonic to biofilm growth transition in Candida albicans. The preferential binding of H3V(CTG) at the biofilm gene promoters makes chromatin repressive for the biofilm mode of growth. The two evolutionarily conserved chaperone complexes involved in incorporating histone H3 are CAF-1 and HIRA. In this study, we sought to identify the chaperone complex(es) involved in loading H3V(CTG). We demonstrate that C. albicans cells lacking either Cac1 or Cac2 subunit of the CAF-1 chaperone complex, exhibit a hyper-filamentation phenotype on solid surfaces and form more robust biofilms than wild-type cells, thereby mimicking the phenotype of the H3V(CTG) null mutant. None of the subunits of the HIRA chaperone complex shows any significant difference in biofilm growth as compared to the wild type. The occupancy of H3V(CTG) is found to be significantly reduced at the promoters of biofilm genes in the absence of CAF-1 subunits. Hence, we provide evidence that CAF-1, a chaperone known to load canonical histone H3 in mammalian cells, is involved in chaperoning of variant histone H3V(CTG) at the biofilm gene promoters in C. albicans. Our findings also illustrate the acquisition of an unconventional role of the CAF-1 chaperone complex in morphogenesis in C. albicans.

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