Akerblad P, Rosberg M, Leanderson T, Sigvardsson M
Immunology Group, CMB, Lund University, S-223 62 Lund, Sweden.
Mol Cell Biol. 1999 Jan;19(1):392-401. doi: 10.1128/MCB.19.1.392.
Early B-cell factor (EBF) is a transcription factor suggested as essential for early B-lymphocyte development by findings in mice where the coding gene has been inactivated by homologous disruption. This makes the identification of genetic targets for this transcription factor pertinent for the understanding of early B-cell development. The lack of B29 transcripts, coding for the beta subunit of the B-cell receptor complex, in pro-B cells from EBF-deficient mice suggested that B29 might be a genetic target for EBF. We here present data suggesting that EBF interacts with three independent sites within the mouse B29 promoter. Furthermore, ectopic expression of EBF in HeLa cells activated a B29 promoter-controlled reporter construct 13-fold and induced a low level of expression from the endogenous B29 gene. Finally, mutations in the EBF binding sites diminished B29 promoter activity in pre-B cells while the same mutations did not have as striking an effect on the promoter function in B-cell lines of later differentiation stages. These data suggest that the B29 gene is a genetic target for EBF in early B-cell development.
早期B细胞因子(EBF)是一种转录因子,通过对编码基因经同源破坏而失活的小鼠的研究发现,它被认为是早期B淋巴细胞发育所必需的。这使得鉴定该转录因子的基因靶点对于理解早期B细胞发育具有重要意义。在EBF缺陷小鼠的前B细胞中缺乏编码B细胞受体复合物β亚基的B29转录本,这表明B29可能是EBF的一个基因靶点。我们在此展示的数据表明,EBF与小鼠B29启动子内的三个独立位点相互作用。此外,EBF在HeLa细胞中的异位表达使B29启动子控制的报告基因构建体激活了13倍,并诱导了内源性B29基因的低水平表达。最后,EBF结合位点的突变降低了前B细胞中B29启动子的活性,而相同的突变对后期分化阶段B细胞系中的启动子功能没有那么显著的影响。这些数据表明,B29基因是早期B细胞发育中EBF的一个基因靶点。