TSA has a complex effect on cell cycle progression

It has been shown for a number of genes that the reversible (de)acetylation of the N-terminal histone tails by specific histone acetylases (HAT) and deacetylases (HDAC) regulates gene expression. Acetylation is thought to decrease the affinity of histones to DNA as well as the interactions between nucleosomes within the chromatin fibre. A number of HDACs can be inhibited by Trichostatin A (TSA) to induce a state of global chromatin acetylation. We have started to study the effect of TSA on the in vivo chromatin organization and on cell cycle progression. First experiments with cells expressing H2A-YFP indicate that TSA induces changes in the chromatin organization of the interphase nucleus and leads to an increase of the YFP fluorescence. The FACS analysis revealed that the effect of TSA on cell cycle progression was strongly dependent on TSA concentration and incubation time. In addition to the G1 and G2/M arrest described previously in the literature we detected a strong block in S phase under certain conditions. TSA caused apoptosis in a concentration dependent manner. The data suggest that various HDACs and/or multiple pathways are involved in the induction of apoptosis. The molecular origin of the TSA induced S block and apoptosis is currently examined by expression profiling.