RNA Polymerase II Dependent Crosstalk between H4K16 Deacetylation and H3K56 Acetylation Promotes Transcription of Constitutively Expressed Genes

Nucleosome dynamics in the coding region of a transcriptionally active locus is critical for understanding how RNA polymerase II progresses through the gene body. Histone acetylation and deacetylation critically influence nucleosome accessibility during DNA metabolic processes like transcription. Effect of such histone modifications is context and residue dependent. Rather than effect of individual histone residues, the network of modifications of several histone residues in combination generates a chromatin landscape that is conducive for transcription. Here we show that in Saccharomyces cerevisiae, crosstalk between deacetylation of the H4 N-terminal tail residue H4K16 and acetylation of the H3 core domain residue H3K56, promotes RNA polymerase II progression through the gene body. Results indicate that deacetylation of H4K16 precedes and in turn induces H3K56 acetylation. Effectively, recruitment of Rtt109, the HAT responsible for H3K56 acetylation is essentially dependent on H4K16 deacetylation. In Hos2 deletion strains, where H4K16 deacetylation is abolished, both H3K56 acetylation and RNA polymerase II recruitment gets significantly impaired. Notably, H4K16 deacetylation and H3K56 acetylation are found to be essentially dependent on active transcription. In summary, H4K16 deacetylation promotes H3K56 acetylation and the two modifications together work towards successful functioning of RNA polymerase II during active transcription.