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

• Published in: International immunology 2008-03, Vol.20 (3), p.453-460
• Main Authors: Ochiai, Kyoko, Muto, Akihiko, Tanaka, Hiromu, Takahashi, Shinichiro, Igarashi, Kazuhiko
• Format: Article
• Language: English
• Subjects: B cells; B-Lymphocytes - immunology; Basic-Leucine Zipper Transcription Factors - immunology; Cell Line; Gene Expression Regulation; gene regulation; Humans; Introns; Maf; MafK Transcription Factor - immunology; Positive Regulatory Domain I-Binding Factor 1; Protein Binding; Protein Interaction Domains and Motifs; Proto-Oncogene Proteins c-bcl-6 - immunology; Repressor Proteins - immunology; transcription factor
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxn005

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.