EBF1 acts as a powerful repressor of Blimp-1 gene expression in immature B cells

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• 作者：Hidehiko Kikuchi^a ; ^{masakari@med.miyazaki-u.ac.jp} ; Masami Nakayama^a ; Yasunari Takami^a ; Futoshi Kuribayashi^b ; Tatsuo Nakayama^a
• 关键词：Ab ; antibody ; AID ; activation-induced deaminase ; Bach2 ; BTB and CNC homology 2 ; Bcl-6 ; B cell lymphoma-6 ; BCR ; B cell receptor ; Blimp-1 ; B lymphocyte-induced maturation protein-1 ; ChIP ; chromatin immunoprecipitation ; CLP ; common lymphoid progenitor ; EBF1
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：15 June, 2012
• 卷：422
• 期：4
• 页码：780-785
• 文件大小：692 K

摘要

The transcription factor, early B cell factor 1 (EBF1) with an atypical zinc-finger and helix-loop-helix motif, is essential for development and differentiation of lymphocytes. In mice, EBF1 is involved in the generation of pre-pro B cells (the first specified progenitors of B cells) from common lymphoid progenitors (CLPs) and transcription regulations of various genes involved in B cell-development, for instance, mb-1 and Pax5. During B lymphopoiesis, interestingly, EBF1 is detected throughout from CLPs to mature B cells. However, in immature B cells, the physiological role of EBF1 remains to be elucidated. Here, by analyzing EBF1-deficient DT40 cells, EBF1^{鈭?鈭?/sup>, generated by us, we show that EBF1-deficiency caused significant increases (to 鈭?00%) in both mRNA and protein levels of B lymphocyte-induced maturation protein-1 (Blimp-1), the master gene for plasma cell differentiation. In addition, both transcription and protein synthesis of Blimp-1 were remarkably down-regulated (to 鈭?0%) by re-expression (over-expression) of EBF1. Chromatin immunoprecipitation assay revealed that EBF1 binds to proximal 5鈥?upstream regions around two putative EBF1 binding motifs of the gene in vivo. These results suggest that EBF1 takes part in transcriptional regulations of the Blimp-1 gene in immature B cells, and may play a key role in B cell differentiation. This is the first report on a novel EBF1 function in immature B cells as a powerful repressor of Blimp-1 gene expression.}