Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning

Abstract

H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed.

Histone H3 Lysine 36 Methylation Antagonizes Silencing in Saccharomyces cerevisiae Independently of the Rpd3S Histone Deacetylase Complex

“…However, of all the genes with decreased expression in a set2D strain (290), only 60 also show decreased expression in an htz1D strain. Consistent with this lack of overlap, htz1D and set2D strains display synthetic lethality (Krogan et al 2003), and H2A.Z and methylated H3-K36 are present in distinct regions of genes (Krogan et al 2003;Guillemette et al 2005;Raisner et al 2005;Rao et al 2005;Pokholok et al 2005;Zhang et al 2005). We conclude that H2A.Z and Set2 antagonize silencing in the same regions of the genome.…”

INO80 subfamily of chromatin remodeling complexes

“…As for the function of H2AZ, this histone variant has been demonstrated to play important roles in transcriptional activation, antagonization of gene-silencing, and chromosome stability (reviewed in [91]). Recently, genome-wide studies demonstrated that yeast Htz1 is globally localized to most of the gene promoters in euchromatin, and generally present in the single nucleosomes flanked a nucleosome-free region that contains the transcription initiation site [82,83,95]. Consistent with previous results, these studies further confirm that the SWR1 complex deposits H2AZ into the genome, probably in a replication independent manner.…”

Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection

“…One interpretation of this result is that Leu3 binding is selected against in regions of high H2A.Z. This could be related to high H2A.Z binding in telomeric regions, or to possible biases in the distribution of H2A.Z in active and inactive promoters (Guillemette et al 2005;Zhang et al 2005). However, the converse weighting scheme, downweighting Leu3 binding sites in high H2A.Z/H2B regions and up-weighting sites in low H2A.Z/H2B regions, has only a marginal effect on AUC-ROC values (the unweighted value of 0.756 improves to 0.768).…”