PHYSIOLOGICAL REGULATORS OF CYTOCHROME OXIDASE GENES

描述：一系列神经、肌肉和视网膜退行性疾病 与广泛的病理条件有关的遗传或 针对线粒体电子传递链的体细胞突变 不同哺乳动物组织的考克斯的特征显示， 催化水平的可预测变化无处不在，但 考克斯Vb亚基在不同组织中的表达不同，低氧条件下， 条件 结果还表明，参与多因素结合 在考克斯Bv表达的组织依赖性变化中的负增强子 以及低氧条件下该基因的转录下调 条件 此外，研究人员还描述了一种新的bHLH 心肌特异性转录激活因子 特异性考克斯VIII（H）基因。 基于此，建议继续 研究了考克斯复合物的生化特性， 不同生理条件下考克斯基因的转录调控 条件如下：1）进一步表征考克斯Bv阴性 增强剂，以了解如何活动，这种消极的 增强子在不同组织中和在肌生成期间被调节。 蛋白 与单个基序（包括YY-1 '，GTG基序）结合的因子 将被纯化，蛋白质之间的分子间相互作用模式 将研究与该区域的四个单独DNA基序的结合。 （二） 缺氧诱导核编码考克斯Bv和Bv基因表达下调的机制 在C2 C12细胞中，MtTFA mRNA和考克斯VIII（H）mRNA的上调将被抑制。 研究以阐明顺式作用DNA元件的性质， 介导这些细胞特异性作用的蛋白质因子。 3)纯化及 心肌特异性bHLH蛋白因子的表征将是 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.