Schanke J T, Marcuzzi A, Podzorski R P, Van Ness B
Department of Biochemistry, University of Minnesota, Minneapolis 55455.
Nucleic Acids Res. 1994 Dec 11;22(24):5425-32. doi: 10.1093/nar/22.24.5425.
Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by trans-acting factors which interact with two distinct enhancer elements. A new protein-DNA interaction has been identified upstream of the intron enhancer, within the matrix-associated region of the J-C intron. The binding activity is greatly inducible in pre-B cells by bacterial lipopolysaccharide and interleukin-1 but specific complexes are found at all stages of B cell development tested. The footprinted binding site is homologous to the consensus AP1 motif. The protein components of this complex are specifically competed by an AP1 consensus motif and were shown by supershift to include c-Jun and c-Fos, suggesting that this binding site is an AP1 motif and that the Jun and Fos families of transcription factors play a role in the regulation of the kappa light chain gene. Mutation of the AP1 motif in the context of the intron enhancer was shown to decrease enhancer-mediated activation of the promoter in both pre-B cells induced with LPS and constitutive expression in mature B cells.
κ免疫球蛋白轻链基因的表达需要由与两个不同增强子元件相互作用的反式作用因子进行发育和组织特异性调控。在J-C内含子的基质相关区域内，已在内含子增强子上游鉴定出一种新的蛋白质-DNA相互作用。细菌脂多糖和白细胞介素-1可在pre-B细胞中极大地诱导结合活性，但在所测试的B细胞发育的所有阶段均发现了特异性复合物。足迹结合位点与共有AP1基序同源。该复合物的蛋白质成分被AP1共有基序特异性竞争，并通过超迁移显示包括c-Jun和c-Fos，这表明该结合位点是一个AP1基序，并且转录因子的Jun和Fos家族在κ轻链基因的调控中起作用。在LPS诱导的pre-B细胞和成熟B细胞的组成型表达中，内含子增强子背景下的AP1基序突变均显示会降低增强子介导的启动子激活。
