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The OBF‐1 gene locus confers B cell‐specific transcription by restricting the ubiquitous activity of its promoter
Author(s) -
Massa Steffen,
Junker Steffen,
Schubart Karin,
Matthias Gabriele,
Matthias Patrick
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200323882
Subject(s) - biology , enhancer , microbiology and biotechnology , promoter , gene , transcription (linguistics) , transcription factor , b cell , locus (genetics) , coactivator , gene expression , genetics , linguistics , philosophy , antibody
Abstract Transcription of the gene encoding the transcriptional coactivator Oct‐binding factor 1 (OBF‐1)/OCA‐B/Bob.1 is largely restricted to B cells. During B cell development OBF‐1 expression shows two peaks, one in immature B cells in the bone marrow and the other in germinal center B cells. Promoter analysis has identified a cAMP response element (CRE)‐binding site present in the OBF‐1 proximal promoter that is crucial for activity in B cells and for the induction of OBF‐1 expression upon stimulation with CD40 ligand/IL‐4. Here we address the question of how transcription of the OBF‐1 gene is restricted to B cells. Surprisingly, in transient transfection assays the OBF‐1 proximal promoter exhibited an equally strong activity in B and non‐B cells. In contrast, upstream promoter regions displayed B cell‐specific properties, partly overlapping with DNaseI hypersensitive sites identified in this study. In mice, expression of a neomycin resistance gene under the control of a Polyoma enhancer/TK promoter cassette was restricted to B cells when integrated into the OBF‐1 locus, but was ubiquitous when integrated into two other loci, Oct‐1 or the large subunit of RNA polymerase II.Therefore, lineage commitment of the OBF‐1 gene is promoter independent and is achieved by regulating the entire locus in a B cell‐specific manner.