The repeating subunit of chromatin, the nucleosome core particle, is intimately associated with DNA. Because of this, it is involved in all DNA-templated processes, including transcriptional regulation. Nucleosomes consist of two copies each of histones H2A, H2B, H3, and H4. In the yeast <i>Saccharomyces cerevisiae</i> H2A.Z is a histone H2A variant that replaces canonical histone H2A in about 10% of nucleosomes. Histone H2A.Z has distinct functions from histone H2A and is involved in transcriptional regulation, DNA damage response, and heterochromatin silencing. Histone H2A.Z-containing nucleosomes serve as a buffer between heterochromatic and euchromatic DNA. In addition, H2A.Z is found in nucleosomes flanking the nucleosome free region of promoters, presumably to establish a transcriptionally ‘poised’ state by destabilizing the nucleosome core particle. Rapamycin is an antifungal drug that inhibits protein synthesis and arrests the cell cycle. We show that rapamycin sensitivity is yeast strain-specific. Deletion of H2A.Z confers an intermediate sensitivity to rapamycin at relatively low concentrations. We find that H2A.Z deletion affects the expression of several genes in protein complexes associated with the target of rapamycin (TOR) signal pathway. We show that loss of H2A.Z exacerbates gene expression irregularities in the presence of rapamycin, likely leading to the intermediate sensitivity and diminished cell growth. Finally, we find that TOR complex members whose expression are affected by loss of H2A.Z have H2A.Z-containing nucleosomes in the promoters. Taken together, we have identified a novel role for histone H2A.Z in resistance to the antifungal drug rapamycin.

Histone H2A variant H2A.Z regulating the expression of TOR signal genes in the yeast <i>Saccharomyces cerevisiae</i>

ACS Spring 2022

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Histone H2A variant H2A.Z regulating the expression of TOR signal genes in the yeast Saccharomyces cerevisiae