Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6
Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6
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DOI：
10.1093/intimm/dxn005
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Igarashi, Kazuhiko
中科院分区：
文献类型：
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作者：
Ochiai, Kyoko;Muto, Akihiko;Igarashi, Kazuhiko
B淋巴细胞诱导成熟蛋白1 （Blimp-1）是浆细胞分化的关键调控因子。在最终分化为浆细胞之前，Blimp-1在B细胞中的表达受到转录抑制因子BTB和CNC同源性2 （Bach2）和B细胞淋巴瘤6 （Bcl6）的抑制。Bach2通过与MafK形成异源二聚体结合到Blimp-1基因上游启动子区Maf识别元件（MARE）上。在B细胞中发现Bach2和Bcl6相互作用。虽然Bach2和Bcl6都具有介导蛋白质相互作用的BTB结构域，但它们以BTB独立的方式相互作用。已知Bcl6通过内含子5中的Bcl6识别元件1抑制Prdm1，其中鉴定了一个假定的进化保守的MARE。两者都抑制含有内含子5区的报告基因的表达，这取决于在18-81 pre-B细胞中各自结合位点的存在。Bach2和Bcl6的共表达导致报告质粒的进一步抑制。染色质免疫沉淀实验显示，在多种B细胞系中，MafK与内含子MARE结合，从而表明它与Bach2作为异源二聚体结合。因此，Bach2和Bcl6之间的相互作用可能对B细胞中Prdm1的适当抑制至关重要。
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.