Epigenetic mechanisms regulate Delta NP73 promoter function in human tonsil B cells

Delta Np73 is an anti-apoptotic product of the TP73 gene whose function in the immune system has not been extensively studied. We analyzed human tonsil B cell subpopulations physically subdivided into resting or activated fractions and found Delta Np73 gene expression essentially in cells bearing features of activation. Moreover, and accordingly, both these fractions proved to be sensitive to treatment in culture with the polyclonal activator TPA that caused substantial increase in Delta Np73 mRNA and protein expression. We also analyzed the TP73 oncogenic-relevant internal promoter 2 (P2) and identified epigenetics as its major regulatory factor since active DNA and histone configurations strictly correlated with Delta Np73 expression upon activation by agents capable of loosening chromatin compaction. Finally, in line with the known TPA pathway, we found that nuclear proteins could bind a sequence corresponding to a unique AP1 site on promoter 2 selectively in the activated cell fraction. Our results suggest a Delta Np73 function in B cell immunity, indicate epigenetics as master TP73 P2 regulator, and point to AP1 site occupancy as playing an putative mechanistic role in this process. (C) 2010 Elsevier Ltd. All rights reserved.