Kozmik Z, Wang S, Dörfler P, Adams B, Busslinger M
Institute of Molecular Pathology, Vienna, Austria.
Mol Cell Biol. 1992 Jun;12(6):2662-72. doi: 10.1128/mcb.12.6.2662-2672.1992.
The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.
CD19蛋白表达于除终末分化浆细胞外的所有B淋巴细胞表面,并被认为是控制增殖和分化的信号转导受体。在此,我们在大量B淋巴细胞系中证明了CD19基因的表达模式与B细胞特异性转录因子BSAP之间完全相关。人CD19基因已被克隆,并且通过体外蛋白质-DNA结合研究确定了几个BSAP结合位点。特别地,在一组异源转录起始位点上游的-30启动子区域中,存在一个高亲和力的BSAP结合位点而非TATA序列。此外,在表达CD19的B细胞系中,该位点在体内被BSAP占据,但在浆细胞或HeLa细胞中则不然。这个高亲和力位点在人和小鼠CD19基因的启动子中均保守,并且在瞬时转染实验中进一步显示它赋予β-珠蛋白报告基因B细胞特异性。另外,发现BSAP是与CD19启动子相互作用的B细胞核提取物中唯一丰富的DNA结合活性。总之,这些证据强烈表明BSAP参与了CD19基因的调控。