Rice Kim L, Kees Ursula R, Greene Wayne K
School of Veterinary and Biomedical Sciences, Division of Health Sciences, Murdoch University, Perth, WA 6150, Australia.
Biochem Biophys Res Commun. 2008 Mar 14;367(3):707-13. doi: 10.1016/j.bbrc.2007.12.005. Epub 2007 Dec 10.
TLX1/HOX11 encodes an NK-like homeodomain transcription factor that is both normally required for embryonic development and aberrantly expressed in T-cell acute lymphoblastic leukemia. Previous studies have shown that TLX1 can regulate target genes including ALDH1A1 and FHL1. However, whereas ALDH1A1 is consistently regulated by TLX1, endogenous FHL1 is only induced in a proportion of fibroblast or T-cell clones stably expressing TLX1. Here, we provide an explanation for these findings by demonstrating that the induction of FHL1, but not ALDH1A1, requires a high level of TLX1 expression in NIH 3T3 cells. In luciferase reporter assays, TLX1-mediated repression rather than activation of the FHL1 gene promoter and the magnitude of this effect was strongly influenced by the cellular background. Together, these results characterize TLX1 as a dual function regulator whose activity in respect to FHL1 is critically dependent upon its cellular concentration, as well as cell type and promoter context.
TLX1/HOX11编码一种NK样同源结构域转录因子，它在胚胎发育中是正常必需的，并且在T细胞急性淋巴细胞白血病中异常表达。先前的研究表明，TLX1可以调节包括ALDH1A1和FHL1在内的靶基因。然而，虽然ALDH1A1始终受TLX1调节，但内源性FHL1仅在一部分稳定表达TLX1的成纤维细胞或T细胞克隆中被诱导。在这里，我们通过证明在NIH 3T3细胞中FHL1（而非ALDH1A1）的诱导需要高水平的TLX1表达，为这些发现提供了解释。在荧光素酶报告基因检测中，TLX1介导的是对FHL1基因启动子的抑制而非激活，并且这种效应的程度受到细胞背景的强烈影响。总之，这些结果将TLX1表征为一种双功能调节因子，其对FHL1的活性关键取决于其细胞浓度以及细胞类型和启动子背景。
