The Yaf9 Component of the SWR1 and NuA4 Complexes Is Required for Proper Gene Expression, Histone H4 Acetylation, and Htz1 Replacement near Telomeres

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Abstract
Yaf9, Taf14, and Sas5 comprise the YEATS domain family in Saccharomyces cerevisiae, which in humans includes proteins involved in acute leukemias. The YEATS domain family is essential, as a yaf9Δ taf14Δ sas5Δ triple mutant is nonviable. We verify that Yaf9 is a stable component of NuA4, an essential histone H4 acetyltransferase complex. Yaf9 is also associated with the SWR1 complex, which deposits the histone H2A variant Htz1. However, the functional contribution of Yaf9 to these complexes has not been determined. Strains lacking YAF9 are sensitive to DNA-damaging agents, cold, and caffeine, and the YEATS domain is required for full Yaf9 function. NuA4 lacking Yaf9 retains histone acetyltransferase activity in vitro, and Yaf9 does not markedly reduce bulk H4 acetylation levels, suggesting a role for Yaf9 in the targeting or regulation of NuA4. Interestingly, yaf9Δ strains display reduced transcription of genes near certain telomeres, and their repression is correlated with reduced H4 acetylation, reduced occupancy by Htz1, and increased occupancy by the silencing protein Sir3. Additionally, the spectra of phenotypes, genes, and telomeres affected in yaf9Δ and htz1Δ strains are significantly similar, further supporting a role for Yaf9 in Htz1 deposition. Taken together, these data indicate that Yaf9 may function in NuA4 and SWR1 complexes to help antagonize silencing near telomeres.