Nimer S, Fraser J, Richards J, Lynch M, Gasson J
Department of Medicine, University of California, Los Angeles, School of Medicine.
Mol Cell Biol. 1990 Nov;10(11):6084-8. doi: 10.1128/mcb.10.11.6084-6088.1990.
The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5'-flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells.
造血生长因子GM-CSF(粒细胞-巨噬细胞集落刺激因子)由活化的而非静止的T淋巴细胞表达。此前,我们将GM-CSF诱导型启动子活性定位于GM-CSF 5'侧翼序列从-53 bp延伸至+37 bp的90 bp区域。为了更精确地鉴定T淋巴细胞中诱导型启动子活性所需的GM-CSF DNA序列,我们在GM-CSF 5'侧翼序列(-57 bp至-24 bp)中包含重复序列CATT(A/T)的区域内进行了诱变。不改变重复的CATT(A/T)序列的突变不会消除诱导型启动子活性,而任一CATT(A/T)重复序列的突变或缺失都会消除T细胞系和原代人T淋巴细胞中的所有诱导型启动子活性。因此,直接重复序列CATT(A/T)的两个拷贝对于T细胞中GM-CSF的丝裂原诱导型表达是必需的。