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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. We find endogenous Pax5 is bound to the FBXO7 promoter in pre-B cells, and that the exogenous expression of Pax5 represses Fbxo7 transcription in early pro-B cells., Highlights • We defined the human FBXO7 promoter, as a conserved promoter region between −1300 and + 100 bp from the start of exon 1. • Two conserved islands of putative transcription factor binding sites were found with 32 putative binding sites identified for 24 different TFs (17 in the distal region; 15 in the proximal region). • ETS factors, ELF4 and ELF1, and Pax5 and c-Myb bind and activate FBXO7 luciferase reporter constructs. • Fbxo7 represses transcription from its own promoter, and this is a ubiquitin ligase-independent effect.