inases that are highly specific for RS domain-containing splicing factors, the DNA topoisomerase I and AKT. However, data addressing the cellular signals that control phosphorylation of SR proteins remain scarce, as well as the specific kinases involved in these effects. Chromatin biology and pre-mRNA splicing have been considered for a long time as two independent fields. However, recently, chromatin structure has been shown to affect both constitutive and alternative splicing, either through the recruitment of splicing factors or through the modulation of RNA polymerase II elongation rate. In addition, two studies have demonstrated that DNA sequences associated with nucleosomes are preferentially located in exons, providing a general concept for how the architecture of genome packaging could influence pre-mRNA splicing. Chromatin structure is highly controlled by post-translational modifications of histone protein tails including phosphorylation or acetylation. These modifications are catalysed by chromatin-modifying enzymes that add or remove specific groups in a reversible way. It was recently reported that two SR proteins, namely SRSF3 and SRSF1, bind histone H3 tail to control cell cycle progression. These data provide the first evidence that SR proteins associate with chromatin, and suggest that they could also be directly targeted by components of chromatin-remodeling complexes. Lysine acetylation is highly regulated through the opposite actions of histone acetyltransferases and histone deacetylases enzymes. Besides histones, an increasing number of cellular proteins are also subjected to lysine acetylation. Recently, a high-resolution mass spectrometry analysis revealed that a large number of acetylation sites are present on proteins implicated in splicing, including SR proteins, and identified PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19828299 the RRM as a major domain for acetylation. These data support the idea that lysine acetylation could regulate the function of SR proteins. & 2011 European Molecular Biology Organization Acetylation controls SRSF2 protein level V Edmond et al In this study, we demonstrate for the first time that an acetylation/phosphorylation network controls the turnover and activity of the splicing factor SRSF2 in response to genotoxic stress. Therefore, besides phosphorylation, lysine acetylation also appears as a crucial post-translational modification of SR proteins. This effect was prevented when 
SRSF2 was neutralized, indicating that SRSF2 is involved in caspase-8 pre-mRNA splicing on BQ123 cisplatin treatment. Of note, caspase-8 was required for apoptosis in this setting, as co-treating cells with cisplatin and the specific cell-permeable caspase-8 inhibitor IETD-CHO significantly decreased the number of apoptotic cells and prevented the decrease of the caspase8L/caspase-8a ratio. Taken together, these results indicate that SRSF2 accumulates on cisplatin treatment and contributes to cisplatin-induced apoptosis. To assess whether acetylation/phosphorylation signalling networks could have a role in this context, we first analysed the acetylated status of SRSF2. Immunoprecipitation experiments demonstrated that SRSF2 acetylation was dramatically lost on cisplatin treatment. This effect was specific of SRSF2 as cisplatin strongly stimulated the acetylation of the transcription factor E2F1, in agreement with previous data. Consistent with the loss of SRSF2 acetylation, immunoblotting and quantitative RTPCR experiments demonstrated that cisplatin induced a si