Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells

Abstract

Fbxo7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where Fbxo7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. Overlap of Pax5 and c-Myb binding sites suggest that these factors bind cooperatively to transactivate the FBXO7 promoter. Although endogenous Pax5 is bound to the FBXO7 promoter in B cells, c-Myb is also required for FBXO7 expression. Our data suggest the interplay of multiple transcription factors regulate the FBXO7 promoter.