Rosmarin A G, Caprio D, Levy R, Simkevich C
Division of Hematology/Oncology, Miriam Hospital, Providence, RI 02906.
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):801-5. doi: 10.1073/pnas.92.3.801.
Normal cellular differentiation is linked to tightly regulated gene transcription. However, the DNA elements and trans-acting factors that regulate transcription in myeloid cells are poorly defined. CD18, the beta chain of the leukocyte integrins, is transcriptionally regulated during myeloid differentiation. The CD18 promoter is active after transfection into myeloid cells. We demonstrate that a region of the CD18 promoter that contains two binding sites for the PU.1 transcription factor is required for activity in myeloid cells. These sites are bound by in vitro translated PU.1 and by PU.1 from myeloid nuclear extracts. Mutagenesis of these sites abrogates binding by PU.1 and substantially decreases promoter activity in myeloid cells. Thus, the leukocyte-specific transcription factor PU.1 is required for myeloid activity of CD18.
正常的细胞分化与严格调控的基因转录相关。然而,在髓系细胞中调控转录的DNA元件和反式作用因子却鲜有明确界定。白细胞整合素的β链CD18在髓系分化过程中受到转录调控。CD18启动子转染至髓系细胞后具有活性。我们证明,CD18启动子中一个含有两个PU.1转录因子结合位点的区域对于其在髓系细胞中的活性是必需的。这些位点能与体外翻译的PU.1以及髓系细胞核提取物中的PU.1结合。这些位点的诱变消除了PU.1的结合,并显著降低了CD18启动子在髓系细胞中的活性。因此,白细胞特异性转录因子PU.1是CD18在髓系细胞中发挥活性所必需的。