Kara C J, Glimcher L H
Department of Cancer Biology, Harvard School of Public Health, Boston, MA.
J Immunol. 1993 Jun 1;150(11):4934-42.
The class II genes of the major histocompatibility complex are a family of genes whose expression is regulated developmentally in cells of the B lineage and by IFN-gamma in many other cell types. Using the approach of in vivo footprinting, which allows for the examination of protein-promoter interactions within intact cells, we demonstrated a transition from unoccupied to occupied to once again unoccupied class II promoters in cell lines representing the developmental pathway of B cells. IFN-gamma treatment of HeLa cells led to increased promoter occupancy of the DR alpha and DR beta promoters at the same sites that are constitutively bound in mature B cells. No IFN-gamma-specific binding site was induced. Additionally, an octamer element in the DR alpha gene displayed preferential binding in B cells. These results demonstrate that changes in the transcription of the class II genes are associated with changes in factor binding at the promoter in vivo. Moreover, given the ubiquity of class II promoter binding proteins, these results suggest that throughout B cell development and upon IFN-gamma stimulation, the accessibility of class II promoter DNA is subject to regulation.
主要组织相容性复合体的II类基因是一个基因家族，其表达在B细胞系细胞中受发育调控，并在许多其他细胞类型中受γ干扰素调控。利用体内足迹法，该方法可用于检测完整细胞内蛋白质与启动子的相互作用，我们在代表B细胞发育途径的细胞系中证明了II类启动子从未被占据到被占据再到再次未被占据的转变。用γ干扰素处理HeLa细胞导致DRα和DRβ启动子在与成熟B细胞中组成性结合的相同位点上的启动子占据增加。未诱导出γ干扰素特异性结合位点。此外，DRα基因中的一个八聚体元件在B细胞中显示出优先结合。这些结果表明，II类基因转录的变化与体内启动子处因子结合的变化相关。此外，鉴于II类启动子结合蛋白的普遍性，这些结果表明，在整个B细胞发育过程中以及在γ干扰素刺激下，II类启动子DNA的可及性受到调控。
