NBPF is a potential DNA-binding transcription factor that is directly regulated by NF-κB

Abstract

The neuroblastoma breakpoint family (NBPF) has been reported to play potential roles in the development of neuroblastoma and human evolution. However, the exact regulation and function of this family is still unknown. In this study, the genes of NBPF family were found to be densely covered by many high-confidence ChIP-Seq peaks of NF-κB. The expressions of NBPF genes were thus deduced to be regulated by this transcription factor. The activities of NF-κB in HeLa, HepG2 and ECa109 cells were then manipulated with NF-κB activator (TNFα) and inhibitors (BAY11-7082 or p65 siRNA), and the expressions of NBPF genes in these cells were checked. As result, it was found that the expressions of NBPF genes were regulated by NF-κB in HeLa and HepG2 cells. Therefore, the genes of NBPF family were identified as new bona fide direct target genes of NF-κB. In addition, NBPF was also identified as a nuclear protein by in silico prediction and immunolocalization. Finally, the bioinformatics analysis revealed that most of NBPF proteins contained classical nuclear localization signals (NLSs) and a conserved DNA-binding domain similar to the transcription factor stat3b/dna complex or stat-1/dna complex in their N-terminals. Therefore, this study concluded that NBPF was nuclear protein that contained classical NLSs and conserved known DNA-binding domain, and its expression was regulated by another important transcription factor, NF-κB. These findings suggest that NBPF may function as DNA-binding transcription factor in nucleus, which provides important new insight into the functions of NBPF genes in the human cells.