Epigenetic mechanisms regulate ΔNP73 promoter function in human tonsil B cells.
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.
Tumor Genetics and Epigenetics, Istituto Nazionale per la Ricerca sul Cancro - IST Genova, Largo R Benzi 10, 16132 Genova, Italy.
Claudio
C
Brigati
Barbara
B
Banelli
Ida
I
Casciano
Angela
A
Di Vinci
Serena
S
Matis
Giovanna
G
Cutrona
Alessandra
A
Forlani
Giorgio
G
Allemanni
Massimo
M
Romani
D000293:Adolescent; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D014066:Palatine Tonsil / Q000166:cytology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D018808:Transcription Factor AP-1; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human