The Histone Variant H2A.Z C-Terminal Domain Has Locus-Specific Differential Effects on H2A.Z Occupancy and Nucleosome Localization.

The incorporation of histone variant H2A.Z into nucleosomes creates specialized chromatin domains that regulate DNA-templated processes, such as gene transcription. In Saccharomyces cerevisiae, the diverging H2A.Z C terminus is thought to provide the H2A.Z exclusive functions. To elucidate the roles of this H2A.Z C terminus genome-wide, we used derivatives in which the C terminus was replaced with the corresponding region of H2A (ZA protein), or the H2A region plus a transcriptional activating peptide (ZA-rII'), with the intent of regenerating the H2A.Z-dependent regulation globally. The distribution of these H2A.Z derivatives indicates that the H2A.Z C-terminal region is crucial for both maintaining the occupation level of H2A.Z and the proper positioning of targeted nucleosomes. Interestingly, the specific contribution on incorporation efficiency versus nucleosome positioning varies enormously depending on the locus analyzed. Specifically, the role of H2A.Z in global transcription regulation relies on its C-terminal region. Remarkably, however, this mostly involves genes without a H2A.Z nucleosome in the promoter. Lastly, we demonstrate that the main chaperone complex which deposits H2A.Z to gene regulatory region (SWR1-C) is necessary to localize all H2A.Z derivatives at their specific loci, indicating that the differential association of these derivatives is not due to impaired interaction with SWR1-C.