Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6

Kyoko Ochiai, Akihiko Muto, Hiromu Tanaka, Shinichiro Takahashi, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

B lymphocyte-induced maturation protein 1 (Blimp-1) is a key regulator for plasma cell differentiation. Prior to the terminal differentiation into plasma cells, Blimp-1 expression is suppressed in B cells by transcription repressors BTB and CNC homology 2 (Bach2) and B cell lymphoma 6 (Bcl6). Bach2 binds to the Maf recognition element (MARE) of the promoter upstream region of the Blimp-1 gene (Prdm1) by forming a heterodimer with MafK. Bach2 and Bcl6 were found to interact with each other in B cells. While both Bach2 and Bcl6 possess the BTB domain which mediates protein-protein interactions, they interacted in a BTB-independent manner. Bcl6 is known to repress Prdm1 through a Bcl6 recognition element 1 in the intron 5, in which a putative, evolutionarily conserved MARE was identified. Both repressed the expression of a reporter gene containing the intron 5 region depending on the presence of the respective binding sites in 18-81 pre-B cells. Co-expression of Bach2 and Bcl6 resulted in further repression of the reporter plasmid. Chromatin immunoprecipitation assays showed MafK to bind to the intron MARE in various B cell lines, thus suggesting that it binds as a heterodimer with Bach2. Therefore, the interaction between Bach2 and Bcl6 might be crucial for the proper repression of Prdm1 in B cells.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalInternational immunology
Volume20
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Keywords

  • B cells
  • Gene regulation
  • Maf
  • Transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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