Turco E, Manfras B J, Ge L, Rudert W A, Trucco M
Department of Pediatrics, University of Pittsburgh, School of Medicine, Children's Hospital, PA 15213.
Immunogenetics. 1990;32(2):117-28. doi: 10.1007/BF00210449.
Expression of HLA class II genes is coordinately regulated by cis-acting elements present in their promoter regions immediately upstream from the 5' end of their transcription start sites. Trans-acting factors from the nuclear proteins of the cell are able to positively or negatively regulate transcription of these genes by binding to highly conserved sequences, called boxes. After cloning the promoter regions of all the transcribed class II B genes present in the cell line Priess, we were able to identify certain protein-box complexes and to determine the affinity of these proteins for their respective boxes by comparing promoter boxes of each gene to those of the other genes. Different nuclear proteins seemed to bind to the X boxes of the different class II B genes tested. In the case of the Y box-protein complexes, the various Y boxes competed with similar affinities. The protein(s) which specifically bound to the DRB1-CCAAT box also bound to DPB1-CCAAT box, but completely failed to bind the homologous box from DQB1. Further, CCAAT box-specific protein(s) did not bind to the Y box of the same gene, excluding the possibility that these proteins just recognize the reverse CCAAT box (ATTGG) present within Y.
HLA II类基因的表达由位于其转录起始位点5'端上游启动子区域中的顺式作用元件协同调控。细胞中的核蛋白反式作用因子能够通过与称为框的高度保守序列结合,对这些基因的转录进行正向或负向调控。在克隆了细胞系Priess中所有转录的II类B基因的启动子区域后,我们能够鉴定出某些蛋白质-框复合物,并通过将每个基因的启动子框与其他基因的启动子框进行比较,来确定这些蛋白质与其各自框的亲和力。不同的核蛋白似乎与所测试的不同II类B基因的X框结合。在Y框-蛋白质复合物的情况下,各种Y框以相似的亲和力相互竞争。特异性结合DRB1 - CCAAT框的蛋白质也与DPB1 - CCAAT框结合,但完全不能与DQB1的同源框结合。此外,CCAAT框特异性蛋白质不与同一基因的Y框结合,排除了这些蛋白质只是识别Y框中存在的反向CCAAT框(ATTGG)的可能性。