Mitotic chromatin structure contributes both to bookmarking and to transcription reduction

Mitosis encompasses key molecular changes including chromatin condensation, nuclear envelope breakdown, and reduced transcription levels. Immediately after mitosis, the interphase chromatin structure is reestablished and transcription resumes. The reestablishment of the interphase chromatin is probably achieved by ‘bookmarking’, i.e., the retention of at least partial information during mitosis. To gain a deeper understanding of the contribution of histone modifications to the mitotic bookmarking process, we merged proteomics, immunofluorescence, and ChIP-seq approaches. We observed a global concordance between the genomic organization of histone modifications in interphase and mitosis, suggesting that the epigenomic landscape may serve as a component of the mitotic bookmarking process. In addition, we observed a profound deacetylation of both H3K9 and H3K27 residues. We identified HDAC3 and Sirt1/6 as the chromatin regulators responsible for the mitotic associated deacetylation, and explored the role of histone deacetylation in transcription reduction during mitosis. Furthermore, by combing small molecules HDACs specific inhibitors with ChIP-seq experiments we identified the role of each HDAC in shaping the genomic distribution of acetylation during mitosis. Altogether, by merging multiple approaches, our study provides evidence to support a model where histone modifications may play a role both in mitotic bookmarking, and in modulating transcription during mitosis.