The MYST HAT Sas2 is part of the SAS-I complex. The target for acetylation by Sas2 is Lys16 of histone H4 (H4 K16Ac). This acetylation site marks euchromatic regions and opposes the spreading of heterochromatin at telomere-proximal regions. Changes of SAS-I-mediated H4 K16Ac on a genome-wide scale comparing wt and sas2∆ cells were investigated in this study. We found a pronounced, genome-wide loss of H4 K16 acetylation in the body of transcribed genes in the absence of Sas2. Furthermore, the influence of Sas2 on gene expression was investigated in RNA expression arrays. H4 K16Ac and H4 in wt and sas2∆ was ChIPed. ChIP experiments were performed three times with independent chromatin preparations.