Shelley C S, Farokhzad O C, Arnaout M A
Department of Medicine, Harvard Medical School, Charlestown, MA 02129.
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5364-8. doi: 10.1073/pnas.90.11.5364.
Human CD11a/CD18 is a noncovalently associated heterodimeric receptor expressed exclusively on the surface of lymphocytes and myeloid cells. To begin to understand the mechanisms that direct the expression of the genes encoding this receptor, we have cloned and characterized the promoter region of the CD11a gene and localized cis-acting elements involved in its expression in lymphoid and myeloid cells. One such element is the "LYM" box, which interacts with two sets of DNA-binding activities, one primarily expressed in lymphocytes and preerythroid cells and the other expressed predominantly in myeloid cells. A second element required for expression of the CD11a gene contains the "GAGA" sequence RRRGAGGAAG (R indicates a purine), which interacts with the DNA-binding activities MS-1 and MS-2. MS-1 is expressed exclusively in myeloid cells and probably represents a member of the Ets family of transcription activators. MS-2 is present in epithelial, preerythroid, and lymphoid cells but is only detected in myeloid cells after differentiation. MS-2 also binds to a second element within the CD11a promoter and homologous elements present in the promoter regions of the CD11b and CD43 genes. Since MS-2 interacts with a number of different gene promoters and is developmentally regulated in myeloid cells, it may play a major role in regulating myeloid gene expression.
人CD11a/CD18是一种非共价结合的异二聚体受体，仅在淋巴细胞和髓细胞表面表达。为了开始了解指导编码该受体的基因表达的机制，我们克隆并鉴定了CD11a基因的启动子区域，并定位了参与其在淋巴细胞和髓细胞中表达的顺式作用元件。其中一个元件是“LYM”框，它与两组DNA结合活性相互作用，一组主要在淋巴细胞和早幼红细胞中表达，另一组主要在髓细胞中表达。CD11a基因表达所需的第二个元件包含“GAGA”序列RRRGAGGAAG（R表示嘌呤），它与DNA结合活性MS-1和MS-2相互作用。MS-1仅在髓细胞中表达，可能代表转录激活因子Ets家族的一个成员。MS-2存在于上皮细胞、早幼红细胞和淋巴细胞中，但仅在分化后的髓细胞中检测到。MS-2还与CD11a启动子内的第二个元件以及CD11b和CD43基因启动子区域中存在的同源元件结合。由于MS-2与许多不同的基因启动子相互作用，并在髓细胞中受到发育调控，它可能在调节髓细胞基因表达中起主要作用。
