Gds1 interacts with NuA4 to promote H4 acetylation at ribosomal protein genes

In our previously published studies, RNA polymerase II transcription initiation complexes were assembled from yeast nuclear extracts onto immobilized transcription templates and analyzed by quantitative mass spectrometry. In addition to the expected basal factors and coactivators, we discovered that the uncharacterized protein Gds1 showed activator-stimulated association with promoter DNA. Gds1 co-precipitated with the histone H4 acetyltransferase NuA4, and its levels often tracked with NuA4 in immobilized template experiments. GDS1 deletion led to reduction in H4 acetylation in vivo and other phenotypes consistent with partial loss of NuA4 activity. Genome-wide chromatin immunoprecipitation revealed that the reduction in H4 acetylation was strongest at ribosomal protein gene promoters and other genes with high NuA4 occupancy. Therefore, while Gds1 is not a stoichiometric subunit of NuA4, we propose that it interacts with and modulates NuA4 in specific promoter contexts. Gds1 has no obvious metazoan homolog, but structural predictions suggest it may be distantly related to the DEK protein.