EBF1 acts as a powerful repressor of Blimp-1 gene expression in immature B cells.
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(-/-), generated by us, we show that EBF1-deficiency caused significant increases (to ∼800%) 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 ∼20%) by re-expression (over-expression) of EBF1. Chromatin immunoprecipitation assay revealed that EBF1 binds to proximal 5'-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.
Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. masakari@med.miyazaki-u.ac.jp
Hidehiko
H
Kikuchi
Masami
M
Nakayama
Yasunari
Y
Takami
Futoshi
F
Kuribayashi
Tatsuo
T
Nakayama
D020121:5' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D016335:Zinc Fingers
D020121:5' Untranslated Regions; D012097:Repressor Proteins