Histone variant H2A.Z plays multiple roles in the maintenance of heterochromatin integrity.
H2A.Z, an evolutionally well-conserved histone H2A variant, is involved in many biological processes. Although the function of H2A.Z in euchromatic gene regulation is well known, its function and deposition mechanism in heterochromatin are still unclear. Here, we report that H2A.Z plays multiple roles in fission yeast heterochromatin. While a small amount of H2A.Z localizes at pericentromeric heterochromatin, loss of methylation of histone H3 at Lys9 (H3K9me) induces the accumulation of H2A.Z, which is dependent on the H2A.Z loader, SWR complex. The accumulated H2A.Z suppresses heterochromatic non-coding RNA transcription. This transcriptional repression activity requires the N-terminal tail of H2A.Z, which is involved in the regulation of euchromatic gene transcription. RNAi-defective cells, in which a substantial amount of H3K9me is retained by RNAi-independent heterochromatin assembly, also accumulate H2A.Z at heterochromatin, and the additional loss of H2A.Z in these cells triggers a further decrease in H3K9me. Our results suggest that H2A.Z facilitates RNAi-independent heterochromatin assembly by antagonizing the demethylation activity of Epe1, an eraser of H3K9me. Furthermore, H2A.Z suppresses Epe1-mediated transcriptional activation, which is required for subtelomeric gene repression. Our results provide novel evidence that H2A.Z plays diverse roles in chromatin silencing.
Tsukii K, Takahata S, Murakami Y