Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity

To study the function of this residue independent from the enzymes that modify it, we used a “histone replacement” system in Drosophila to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. Post-translational modification of histone H3K36 is neither required to suppress cryptic transcription initiation nor to include alternative exons in Drosophila; instead it promotes expression of active genes by stimulating polyadenylation. Overall design: Examination of poly-A RNA-seq, total nuclear RNA-seq, Start-seq, and ATAC-seq from HWT and K36R rescue larvae