Abstract
In Saccharomyces cerevisiae the histone H2A variant H2A.Z
replaces H2A in about 10% of nucleosomes. H2A.Z is involved in all
DNA-templated processes including transcriptional regulation. H2A.Z is
found in nucleosomes flanking the nucleosome free region of promoters.
While deletion of HTZ1 in S. cerevisiae leads to rapamycin
sensitivity, the molecular mechanism behind this sensitivity is not well
understood. Here we show that rapamycin sensitivity is yeast
strain-specific. When treated with rapamycin, the htz1D strain is
unable to properly express several genes found in Target Of Rapamycin
protein complexes as well as genes whose expression are critical for
amino acid uptake by yeast, including GAP1 and GTR1. We
also find an epistatic relationship between HTZ1 and GTR1
(whose protein product is a member of the exit from rapamycin-induced
growth arrest complex and a GTPase that is required for the proper
activation of the Tor1 kinase. Although GTR1 is normally
upregulated in the presence of rapamycin, overexpression of GTR1
does not rescue the sensitivity phenotype seen in the htz1D
strain. Additionally, the phosphorylation of downstream targets of the
protein kinase A is affected in the htz1D strain. Gene expression
defects, coupled with disrupted protein kinase A signaling pathway
combine to make the htz1D strain sensitive to rapamycin. Our
study has identified a novel role for histone H2A.Z in regulating both
the TOR and PKA signal pathways.