Epigenetic mechanisms regulate ΔNP73 promoter function in human tonsil B cells

Claudio Brigati, Barbara Banelli, Ida Casciano, Angela Di Vinci, Serena Matis, Giovanna Cutrona, Alessandra Forlani, Giorgio Allemanni, Massimo Romani

Research output: Contribution to journalArticle

Abstract

ΔNp73 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 ΔNp73 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 ΔNp73 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 ΔNp73 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 ΔNp73 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.

Original languageEnglish
Pages (from-to)408-414
Number of pages7
JournalMolecular Immunology
Volume48
Issue number4
DOIs
Publication statusPublished - Jan 2011

Keywords

  • B-cells
  • DNA methylation
  • Epigenetics
  • TP73

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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    Brigati, C., Banelli, B., Casciano, I., Di Vinci, A., Matis, S., Cutrona, G., Forlani, A., Allemanni, G., & Romani, M. (2011). Epigenetic mechanisms regulate ΔNP73 promoter function in human tonsil B cells. Molecular Immunology, 48(4), 408-414. https://doi.org/10.1016/j.molimm.2010.09.001