Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.

Academic Article

Abstract

  • Immunoglobulin rearrangement from variable heavy chain (V(H)) to diversity (D)-joining heavy chain (J(H)), which occurs exclusively in B lineage cells, is impaired in mice deficient for the B lineage-specific transcription factor Pax5. Conversely, ectopic Pax5 expression in thymocytes promotes the rearrangement of D(H)-proximal V(H)7183 genes. In exploring the mechanism for Pax5 regulation of V(H)-to-DJ(H) recombination, we have identified multiple Pax5 binding sites in the coding regions of human and mouse V(H) gene segments. Pax5 bound to those sites in vitro and occupied V(H) genes in early human and mouse B lineage cells. Moreover, Pax5 interacted with the recombination-activating gene 1 (RAG1)-RAG2 complex to enhance RAG-mediated V(H) recombination signal sequence cleavage and recombination of a V(H) gene substrate. These findings indicate a direct activating function for Pax5 in RAG-mediated immunoglobulin V(H)-to-DJ(H) recombination.
  • Authors

    Published In

  • Nature Immunology  Journal
  • Keywords

  • Animals, Binding Sites, Cell Lineage, DNA-Binding Proteins, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genes, Immunoglobulin, Homeodomain Proteins, Humans, Immunoglobulin Joining Region, Immunoglobulin Variable Region, Mice, Mice, Mutant Strains, Nuclear Proteins, PAX5 Transcription Factor, Protein Interaction Mapping, Transcriptional Activation
  • Digital Object Identifier (doi)

    Pubmed Id

  • 12401794
  • Author List

  • Zhang Z; Espinoza CR; Yu Z; Stephan R; He T; Williams GS; Burrows PD; Hagman J; Feeney AJ; Cooper MD
  • Start Page

  • 616
  • End Page

  • 624
  • Volume

  • 7
  • Issue

  • 6