Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation

Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re-activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and Bromodomain Protein 4 (BRD4) were recruited to the locus in a different sequential order upon interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 lysine 5 acetylation (H4K5Ac) on the previously activated locus. BRD4 accelerated the dynamics of mRNA synthesis by de-compacting chromatin and hence facilitating transcriptional reactivation. Together, using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism.