MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone α-subunit gene expression
MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone α-subunit gene expression
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DOI：
10.1074/jbc.274.51.36159
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发表时间：
1999-12-17
影响因子：
4.8
通讯作者：
Maurer, RA
中科院分区：
文献类型：
--
作者：
Glenn, DJ;Maurer, RA
糖蛋白激素cr亚单位基因的组织特异性表达涉及一种被称为垂体糖蛋白基础元件的增强子元件，它与LIM同源结构域转录因子LHX2相互作用。当与GAL4 DNA结合域融合时，LHX2的LIM结构域包含一个转录激活结构域。此外，在铜亚单位报告基因的背景下，GAL4结合位点取代了垂体糖蛋白的基本元件，LIM结构域促进了基础转录和RAS介导的转录。此外，当ELK1的LHX2 LIM结构域和反式激活结构域针对一个最小的报告基因时，观察到对RAS激活的协同反应。酵母菌双杂交鉴定了最近描述的黑素细胞特异性基因相关基因1(MRG1)是一种LHX2 LIM相互作用蛋白。体外实验表明MRG1能与LHX2结合，免疫共沉淀实验证明在αT3-1细胞中内源性MRG1与LHX2形成复合体。在αT3-1细胞中表达MRG1可增强cr亚单位报告基因的活性。在体外，MRG1还被证明与TATA结合蛋白和转录辅助激活因子p300结合。这些数据表明了一种模型，在该模型中，LHX2 LIM结构域通过与MRG1相互作用激活转录，导致p300/CBP和TATA结合蛋白的招募。
Tissue-specific expression of the cr-subunit gene of glycoprotein hormones involves an enhancer element designated the pituitary glycoprotein basal element, which interacts with the LIM homeodomain transcription factor, Lhx2, In the present studies we have explored the function of the LIM domain of Lhx2 in stimulating ct-subunit transcription. When fused to the GAL4 DNA-binding domain, the LIM domain of Lhx2 was shown to contain a transcriptional activation domain. Furthermore, in the context of an cu-subunit reporter gene in which a GAL4-binding site replaced the pituitary glycoprotein basal element, the LIM domain enhanced both basal and Ras-mediated transcription. In addition, a synergistic response to Ras activation was observed when the Lhx2 LIM domain and the transactivation domain of Elk1 are directed to a minimal reporter gene. A yeast two-hybrid screen identified the recently described melanocyte-specific gene-related gene 1 (MRG1) as an Lhx2 LIM-interacting protein. MRG1 was shown to bind Lhx2 in vitro, and a co-immunoprecipitation assay provided evidence that endogenous MRG1 forms a complex with Lhx2 in alpha T3-1 cells. Expression of MRG1 in alpha T3-1 cells enhanced cr-subunit reporter gene activity. MRG1 was also shown to bind in vitro to the TATA-binding protein and the transcriptional coactivator, p300. These data suggest a model in which the Lhx2 LIM domain activates transcription through interaction with MRG1 leading to recruitment of p300/CBP and the TATA-binding protein.