B cell-specific activator protein prevents two activator factors from binding to the immunoglobulin J chain promoter until the antigen-driven stages of B cell development.
The immunoglobulin J chain gene is inducibly transcribed in mature B cells upon antigen recognition and a signal from interleukin-2 (IL-2). B cell-specific activator protein (BSAP), a transcription factor that silences J chain transcription, has been identified as a nuclear target of the IL-2 signal. The levels of BSAP progressively decrease in response to IL-2 and this change correlates with the differentiation of B cells into antibody secreting plasma cells. Here we report the binding of the upstream stimulatory factor (USF) to an E-box motif immediately upstream from the BSAP site on the J chain promoter. Mutations in the USF binding motif significantly decrease J chain promoter activity in J chain expressing B cell lines. We also show that a functional relationship exists between USF and a second J chain positive-regulating factor, B-MEF2, using co-immunoprecipitation assays and transfections. Finally, we provide evidence that the binding of BSAP prevents USF and B-MEF2 from interacting with the J chain promoter during the antigen-independent stages of B cell development. It is not until the levels of BSAP decrease during the antigen-driven stages of B cell development that both USF and B-MEF2 are able to bind to their respective promoter elements and activate J chain transcription.
Wallin
J J
JJ
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Rinkenberger
J L
JL
Rao
S
S
Gackstetter
E R
ER
Koshland
M E
ME
Zwollo
P
P
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000276:immunology; D007144:Immunoglobulin J-Chains / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology*; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D014162:Transfection; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; D007376:Interleukin-2; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse