PHYSIOLOGICAL REGULATORS OF CYTOCHROME OXIDASE GENES

描述：多种神经、肌肉和视网膜退行性疾病 广泛的病理情况与遗传性或 针对线粒体电子传递链的体细胞突变 来自不同哺乳动物组织的COX的特征表明 无处不在的、但可变的催化水平的可预测变化 COX VB亚基在不同组织和低氧条件下的表达差异 条件。结果还表明，多因素结合参与了 环氧合酶BV表达的组织依赖性变化中的负性增强子 以及在低氧条件下基因转录下调。 条件。此外，研究人员还描述了一种新型的bHLH 心肌特异转录激活中的因子 特异性COX VIII(H)基因。在此基础上，建议继续 COX复合体和COX复合体的生化特性研究 不同生理条件下COX基因的转录调控 条件如下：1)COX BV阴性的进一步表征 以期了解增强剂这种负性的活性是如何 增强子在不同的组织和肌肉发生过程中都受到调节。蛋白 与单个基序结合的因子(包括YY-1‘，GTG基序) 将被提纯和蛋白质分子间相互作用的模式 将研究与该区域四个单独的DNA基序的结合。2) 低氧诱导核编码COX-BV和BV下调的机制 C2C12细胞MtTFA mRNAs和COX VIII(H)mRNAs表达上调 调查以阐明顺式作用DNA元件的性质和 调节这些细胞特异性效应的蛋白质因素。3)提纯和 心肌特异的bHLH蛋白因子的特征将是 继续使用DNA亲和层析和酵母双杂交 选拔制度。

DESCRIPTION: A number of neural, muscular and retinal degenerative diseases with wide ranging pathological conditions are associated with inherited or somatic mutations targeted to the mitochondrial electron transport chain characterization of COX from different mammalian tissues showed a predictable change in the catalytic levels of ubiquitous, but variably expressed COX Vb subunit varied in different tissues and under hypoxic conditions. Results also suggest the involvement of a multi-factor binding negative enhancer in the tissue dependent variations of COX Bv expression and also in the transcription down regulation of the gene under hypoxic conditions. Additionally, the investigators have characterized a novel bHLH factor in the cardiac muscle specific transcription activation of the muscle specific COX VIII (H) gene. Based on this, it is proposed to continue studies on the biochemical characterization of the COX complex and transcription regulation of COX genes under different physiological conditions as follows: 1) Further characterization of the COX Bv negative enhancer with a view to understand how the activity of this negative enhancer is modulated in different tissues and during myogenesis. Protein factors binding to the individual motifs (including the YY-1', GTG motifs) will be purified and the mode of intermolecular interaction between proteins binding to four individual DNA motifs of this region will be studied. 2) Mechanisms of hypoxia-induced down regulation of nuclear encoded COX Bv and MtTFA mRNAs, and upregulation of COX VIII (H) mRNA in C2C12 cells will be investigated to elucidate the nature of cis-acting DNA elements and the protein factors mediating these cell specific effects. 3) Purification and characterization of the cardiac muscle specific bHLH protein factor will be continued using DNA affinity chromatography and the Yeast two-hybrid selection system.