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

Biochem Biophys Res Commun. 2021 May 21:554:41-48. doi: 10.1016/j.bbrc.2021.03.052. Epub 2021 Mar 25.

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. 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.

Keywords: B cells; ELF4; Fbxo7; Pax5; Promoter; Transcription factor; c-Myb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Base Sequence
  • Binding Sites
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Conserved Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism
  • Humans
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • ELF4 protein, human
  • F-Box Proteins
  • FBXO7 protein, human
  • MYB protein, human
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Proto-Oncogene Proteins c-myb
  • Transcription Factors