Zhuang Fengfeng, Nguyen Manuel P, Shuler Charles, Liu Yi-Hsin
Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DVRC314, Los Angeles, CA 90033, USA.
Biochem Biophys Res Commun. 2009 Apr 3;381(2):241-6. doi: 10.1016/j.bbrc.2009.02.016. Epub 2009 Feb 11.
Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.
先前的研究表明,Msx蛋白主要通过抑制机制来控制基因转录。然而,使用功能获得型或功能缺失型突变体进行的基因表达研究揭示了许多基因靶点,其表达需要功能性Msx蛋白。迄今为止,由于缺乏响应性启动子,对Msx依赖性反式激活机制的研究受到了阻碍。在此,我们证明了小鼠Hspa1b启动子在探究Msx依赖性基因激活机制方面的有用性。我们表明,Msx蛋白通过其C末端结构域激活Hspa1b启动子。这种激活绝对依赖于热休克元件,并且Msx蛋白与热休克因子之间的物理相互作用可能起到一定作用。