The histone variant H2A.Z in yeast is almost exclusively incorporated into the +1 nucleosome in the direction of transcription

Abstract

Transcription start sites (TSS) in eukaryotes are characterized by a nucleosome-depleted region (NDR), which appears to be flanked upstream and downstream by strongly positioned nucleosomes incorporating the histone variant H2A.Z. H2A.Z associates with both active and repressed TSS and is important for priming genes for rapid transcriptional activation. However, the determinants of H2A.Z occupancy at specific nucleosomes and its relationship to transcription initiation remain unclear. To further elucidate the specificity of H2A.Z, we determined its genomic localization at single nucleosome resolution, as well as the localization of its chromatin remodelers Swr1 and Ino80. By analyzing H2A.Z occupancy in conjunction with RNA expression data that captures promoter-derived antisense initiation, we find that H2A.Z’s bimodal incorporation on either side of the NDR is not a general feature of TSS, but is specifically a marker for bidirectional transcription, such that the upstream flanking −1 H2A.Z-containing nucleosome is more appropriately considered as a +1 H2A.Z nucleosome for antisense transcription. The localization of H2A.Z almost exclusively at the +1 nucleosome suggests that a transcription-initiation dependent process could contribute to its specific incorporation.

Genome-wide chromatin accessibility is restricted by ANP32E

“…While it is possible that this occurred through disruption of targeted H2A.Z eviction, no mechanism for ANP32E targeting has been described. On the contrary, targeted H2A.Z installation is known to occur specifically at the NDRs and at the +1 nucleosome position 11 , 36 , 37 , 58 . Therefore, rather than invoking H2A.Z eviction, we favor a simpler explanation for how H2A.Z accumulated at the −1 position.…”

The chromatin remodeler Ino80 mediates alternative RNAPII pausing site determination

“…S2G, Left). Moreover, the distance of pausing site shift in Ino80p-KD showed no significant correlation with H2A.Z Htz1 enrichment in the +1 nucleosome, which is calculated from an existing MNase-ChIP-seq ( 38 ) (fig. S2G, Right).…”

Deciphering the Enigma of the Histone H2A.Z-1/H2A.Z-2 Isoforms: Novel Insights and Remaining Questions

“…In this regard, a good closing example of this is provided by two very recent seemingly contradictory reports which have come up at the time of writing this review. In the first, it is indicated that in yeast, H2A.Z is almost exclusively incorporated into the +1 nucleosome in the direction of transcription, suggesting that H2A.Z has a causative role in the transcription initiation process at this location [99]. In the second, using H2A.Z KO post-mitotic muscle cells, it is shown that this histone variant is neither required to maintain nor to activate transcription which would be in line with the concept that H2A.Z is not a direct player but rather a marker of transcription [11,100].…”