Little is known about the functional relevance of global differences in histone modification levels between cell types, such as normal and cancer cells, but this study suggests that global changes in histone acetylation are involved in the regulation of intracellular pH. The authors showed that global histone deacetylation, which is catalysed by histone deacetylases, takes place as the pH inside cells decreases. The released acetate anions are transported out of the cell by a mechanism that involves concomitant export of protons, preventing pH from falling further.