The role of specific HAT-HDAC interactions in transcriptional elongation

We previously reported genome-wide evidence that the Gcn5 histone acetyltransferase (HAT) is located in the transcribed region of highly expressed genes and that it plays an important role in transcriptional elongation in the fission yeast, Schizosaccharomyces pombe (EMBO Reports 2009; 10:1009-14). Furthermore, the specific interplay between Gcn5 and the Clr3 histone deacetylase (HDAC) controls the acetylation levels of lysine-14 in histone H3 in the same class of highly expressed genes. Mutants of histone H3 that cannot be acetylated at residue 14 show similar stress phenotypes to those observed for mutants lacking Gcn5. In this Extra View article we review these findings in relation to related literature and extend important aspects of the original study. Notably, Gcn5 and Gcn5-dependent acetylation of histone H3K14 tend to be more enriched in the upstream regions of genes that require Gcn5 for correct expression compared to genes that are independent of Gcn5. This suggests a critical role of Gcn5 in the transcriptional initiation of these genes. Gcn5 is however most highly enriched in the transcribed regions of these gene sets but there is no difference between Gcn5-dependent and Gcn5-independent gene sets. Thus we suggest that Gcn5 plays an important but redundant role in the transcriptional elongation of these genes. The Sir2 HDAC has a similar genomic localization and enzymatic activity to Clr3. We studied gcn5Deltasir2Delta double mutants that do not show a suppressed phenotype in relation to gcn5Delta single mutants, compared to gcn5Deltaclr3Delta mutants that do, in order to better understand the specificity of the interplay between Gcn5 and Clr3. In some classes of non-highly expressed genes the clr3Delta mutant tends to restore levels of histone H3K14 acetylation in the double mutant strain more effectively than sir2Delta.