Fig. 3

a Schematic representation of the possible BRD4 functions in telomere elongation. Increased histone acetylation and H2AX phosphorylation accumulate on telomeres, promoting BRD4 binding that in turn facilitates the assembly of telomere protection complex and promotes the activity of Telomerase. Since post-translational modification plays a fundamental role in telomere complexes regulation, it is likely that the kinase and/or the actetyltransferase function of BRD4 may take part to this process. For example, BRD4 may further promote acetylation of histone in the telomeric regions (red arrow) which in turn promotes telomere elongation. In addition, BRD4 may directly affect the acetylation (green arrow) or phosphorylation (blue arrow) of telomerase or other proteins of the telomere protection complex, promoting their activity. Indeed, TERT phosphorylation has been shown to be required for telomerase activation. b Effect of BETi on telomere regulation. BETi compete with acetylated histones for the binding at the BRD4 bromodomains releasing BRD4 from short telomere, destabilizing telomere protection complex organization and reducing Telomerase activity. The progressive shortening of telomere leads cancer cells to senescence or cell death. This structural effect in addition with the cancer specific effect of BRD4 on TERT promoter regulation may represent a possible strategy to target Telomerase function selectively in cancer cells or a strategy to improve telomerase inhibitors efficacy