Regulation of mouse CD72 gene expression during B lymphocyte development.
CD72 is a 45-kDa transmembrane glycoprotein that is predominantly expressed on cells of the B lineage except plasma cells. Previously, we identified the 255-bp minimal mouse CD72 promoter capable of tissue-specific and developmental stage-specific expression. DNase I footprinting analysis of the 255-bp CD72 promoter revealed three protected elements, footprint (FP) I, FP II, and FP III. FP II, which extends from nucleotide -189 to -169 of the mouse CD72 promoter, exhibited both tissue-specific and developmental stage-specific activity that was reflective of the activity of the CD72 gene in vivo. In this report, we show that FP II is specifically recognized by the transcription factor B cell-specific activator protein (BSAP). Mutations eliminating the binding of BSAP in reporter constructs also eliminated the increase of reporter activity in B cells. In addition, cotransfections with reporter constructs plus different amounts of expression plasmids for BSAP showed that CD72 promoter activity was up-regulated by BSAP in plasmacytoma cells and T cells in a dose-dependent manner. Moreover, the expression level of CD72 decreased 10-fold on normal plasma cells. Compared with the presence of BSAP binding in mature B cells, the binding of BSAP was undetectable in those plasma cells. This study strongly suggests that BSAP-FP II interaction plays a critical role in determining the cell-type specificity of the CD72 promoter. The absence of positive factors such as BSAP accounts for at least part of the loss of mouse CD72 expression in plasma cells and thus might be common for the down-regulation of many molecules at the plasma cell stage.
Ying
H
H
Department of Medicine, Stanford University School of Medicine, CA 94305-5487, USA.
Healy
J I
JI
Goodnow
C C
CC
Parnes
J R
JR
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C064228:CD72 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors