Farrance I K, Mar J H, Ordahl C P
Department of Anatomy, University of California, San Francisco 94143-0452.
J Biol Chem. 1992 Aug 25;267(24):17234-40.
M-CAT binding factor (MCBF) governs the activity of the cardiac troponin T gene promoter. M-CAT motifs have also been implicated recently in the regulation of other contractile protein genes which like cardiac troponin T, do not require direct interaction with MyoD1 or related factors for activity. Mutational analysis of the M-CAT motif revealed that it can be functionally replaced by a regulatory motif of the SV40 enhancer which binds human transcription factor TEF-1. Biochemical analyses show that MCBF from muscle nuclei is indistinguishable from TEF-1 in terms of specificity of binding site recognition, fractionation on DNA-agarose, and apparent molecular weight. In addition, antibodies raised against amino- and carboxyl-terminal regions of human TEF-1 also bind to MCBF from chicken muscle. We conclude, therefore, that MCBF is closely related to TEF-1. Finally, MCBF/TEF-1 is highly enriched in the nuclei of striated muscle, as compared with other tissues, consistent with a role in muscle-specific promoter regulation.
M-CAT结合因子(MCBF)调控心肌肌钙蛋白T基因启动子的活性。最近,M-CAT基序也参与了其他收缩蛋白基因的调控,这些基因与心肌肌钙蛋白T一样,其活性不需要与MyoD1或相关因子直接相互作用。对M-CAT基序的突变分析表明,它可以在功能上被SV40增强子的一个调控基序取代,该调控基序可结合人类转录因子TEF-1。生化分析表明,来自肌肉细胞核的MCBF在结合位点识别特异性、在DNA琼脂糖上的分级分离以及表观分子量方面与TEF-1没有区别。此外,针对人类TEF-1氨基末端和羧基末端区域产生的抗体也能与鸡肌肉中的MCBF结合。因此,我们得出结论,MCBF与TEF-1密切相关。最后,与其他组织相比,MCBF/TEF-1在横纹肌细胞核中高度富集,这与它在肌肉特异性启动子调控中的作用一致。