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首页> 外文期刊>Molecular and Cellular Biology >The myeloid-cell-specific c-fes promoter is regulated by Sp1, PU.1, and a novel transcription factor.
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The myeloid-cell-specific c-fes promoter is regulated by Sp1, PU.1, and a novel transcription factor.

机译：髓细胞特异性c-fes启动子受Sp1，PU.1和新型转录因子调控。

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The protein product of the c-fps/fes (c-fes) proto-oncogene has been implicated in the normal development of myeloid cells (macrophages and neutrophils). mRNA for c-fes has been detected exclusively in myeloid cells and vascular endothelial cells in adult mammals. Although a 13-kilobase-pair (kb) human c-fes transgene exhibits high levels of expression in mice, the sequences that confer myeloid-cell-specific expression of the human c-fes gene have not been defined. Transient-transfection experiments demonstrated that plasmids containing 446 bp of c-fes 5'-flanking sequences linked to a luciferase reporter gene were active exclusively in myeloid cells. No other DNA element within the 13-kb human c-fes locus contained positive cis-acting elements, with the exception of a weakly active region within the 3'-flanking sequences. DNase I footprinting assays revealed four distinct sites that bind myeloid nuclear proteins (-408 to -386, -293 to -254, -76 to -65, and -34 to +3). However, the first two footprints resided in sequences that were largely dispensable for transient activity. Plasmids containing 151 bp of 5'-flanking sequences confer myeloid-cell-specific gene expression. Electrophoretic mobility shift analyses demonstrated that the 151-bp region contains nuclear protein binding sites for Sp1, PU.1, and/or Elf-1, and a novel factor. This unidentified factor binds immediately 3' of the PU.1/Elf-1 sites and appears to be myeloid cell specific. Mutation of the PU.1/Elf-1 site or the 3' site (FP4-3') within the context of the c-fes promoter resulted in substantially reduced activity in transient transfections. Furthermore, transient-cotransfection assay demonstrated that PU.1 (and not Elf-1) can transactivate the c-fes promoter in nonmyeloid cell lines. We conclude that the human c-fes gene contains a strong myeloid-cell-specific promoter that is regulated by Sp1, PU.1, and a novel transcription factor.
机译：c-fps / fes（c-fes）原癌基因的蛋白质产物与髓样细胞（巨噬细胞和嗜中性粒细胞）的正常发育有关。仅在成年哺乳动物的髓样细胞和血管内皮细胞中检测到c-fes的mRNA。尽管13碱基对（kb）的人c-fes转基因在小鼠中表现出高水平的表达，但尚未定义赋予人c-fes基因髓样细胞特异性表达的序列。瞬时转染实验表明，与荧光素酶报道基因连接的，包含446 bp c-fes 5'侧翼序列的质粒仅在髓样细胞中具有活性。 13kb人c-fes基因座中的其他DNA元件均不包含正顺式作用元件，但3'侧翼序列中的弱活性区域除外。 DNase I足迹测定法揭示了四个与髓核蛋白结合的不同位点（-408至-386，-293至-254，-76至-65和-34至+3）。但是，前两个足迹位于序列中，对于瞬时活动而言，这些序列在很大程度上是可有可无的。含有151 bp的5'侧翼序列的质粒可赋予骨髓细胞特异性基因表达。电泳迁移率变化分析表明，该151bp区域包含Sp1，PU.1和/或Elf-1的核蛋白结合位点，以及一个新因子。该未知因子立即与PU.1 / Elf-1位点的3'结合，并且似乎是髓样细胞特异性的。在c-fes启动子范围内PU.1 / Elf-1位点或3'位点（FP4-3'）的突变导致瞬时转染中活性大大降低。此外，瞬时共转染试验表明，PU.1（而非Elf-1）可以在非骨髓细胞系中激活c-fes启动子。我们得出的结论是，人类c-fes基因包含一个受Sp1，PU.1和新型转录因子调控的强髓细胞特异性启动子。

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