Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6.
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.
Ochiai
Kyoko
K
Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.
Muto
Akihiko
A
Tanaka
Hiromu
H
Takahashi
Shinichiro
S
Igarashi
Kazuhiko
K
D001402:B-Lymphocytes / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D050985:MafK Transcription Factor / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*
C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C494695:MAFK protein, human; D050985:MafK Transcription Factor; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1