Sherman P A, Basta P V, Heguy A, Wloch M K, Roeder R G, Ting J P
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1989 Sep;86(17):6739-43. doi: 10.1073/pnas.86.17.6739.
The human class II gene, HLA-DR alpha, contains an octanucleotide sequence ATTTGCAT located approximately 40 base pairs upstream of the transcription initiation site. We have investigated the transcriptional function of the DR alpha octamer in human B-lymphoblastoid cells and non-B cells. Deletion and substitution mutagenesis of the octamer sequence greatly reduced the activity of the DR alpha promoter in both in vivo and in vitro cell-free transcription systems of B-cell origin. Conversely, these mutations did not affect promoter activity in several non-B-cell lines that express the DR alpha gene. Removal of octamer-binding proteins by in vivo titration with an octamer-containing competitor plasmid reduced DR alpha promoter activity in B-lymphoblastoid cells. These results suggest that a protein-octamer interaction, most likely involving the B-cell-specific octamer binding protein (OTF-2), is required for DR alpha promoter function in B-lymphoblastoid cells but not in non-B cells.
人类II类基因HLA - DRα在转录起始位点上游约40个碱基对处含有一个八核苷酸序列ATTTGCAT。我们已经研究了DRα八聚体在人B淋巴母细胞和非B细胞中的转录功能。八聚体序列的缺失和替换诱变在源自B细胞的体内和体外无细胞转录系统中都大大降低了DRα启动子的活性。相反,这些突变并不影响在几个表达DRα基因的非B细胞系中的启动子活性。通过用含八聚体的竞争性质粒进行体内滴定去除八聚体结合蛋白,降低了B淋巴母细胞中DRα启动子的活性。这些结果表明,蛋白质 - 八聚体相互作用,很可能涉及B细胞特异性八聚体结合蛋白(OTF - 2),是B淋巴母细胞中DRα启动子功能所必需的,但在非B细胞中并非如此。