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Distinct and overlapping roles for canonical and variant histone H3 lysine 36 in polycomb silencing and global gene regulation

ABSTRACT: Polycomb silencing epigenetically defines cell-type specific gene expression programs through heritable silencing of target genes. Trimethylation of histone H3 lysine 27 (H3K27me3) is essential for this process. Proper positioning of H3K27 into the active site of its cognate methyltransferase, Enhancer of zeste, E(z), is thought to require an unmodified H3K36 residue in cis. Hence, mutation of H3K36 should elicit strong Polycomb phenotypes. Contrary to this expectation, Drosophila mutants of the replication-dependent histone H3 genes (H3.2K36R) display mild Polycomb phenotypes. We hypothesized that the replication-independent H3.3 protein might play a redundant role. By generating an H3.3K36R allele and comparing individual and combined (H3.3K36R/H3.2K36R) mutant animals, we found that H3.2K36 preferentially regulates H3K27me3 levels, whereas H3.2K36 and H3.3K36 carry out homeobox (Hox) repression via distinct mechanisms. Unexpectedly, the robust derepression of Hox genes in the combined H3.2/H3.3K36R mutants does not extend globally to other H3K27me3 marked genes.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE196114 | GEO | 2026/09/30

REPOSITORIES: GEO

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Distinct roles for canonical and variant histone H3 lysine 36 in polycomb silencing

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