CO-ACTIVATORS AND REPRESSORS OF MUSCLE TRANSCRIPTION

肌肉转录的共激活因子和抑制因子

• 批准号: 6338741
• 负责人: LAURENCE H KEDES
• 金额: $ 13.07万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338741
• 关键词: calcium binding protein; congenital oral /facial /cranial defect; developmental genetics; genetic library; genetic mapping; genetic transcription; laboratory mouse; mammalian embryology; molecular cloning; myogenesis; northern blottings; protein binding; protein protein interaction; tissue /cell culture; transcription factor; transfection; yeast two hybrid system

The overall hypothesis to be tested is that Twist is involved in negative regulation of myogenesis by interfering with required transcriptional coregulators, in particular p300 and/or PCAF, and by interacting with other regulators of early myogenic differentiation, such as Msx. This hypothesis will be tested by molecular genetic as well as biochemical analysis of a) mechanisms by which mouse Twist influences the transcription activation, by MEF2 and bHLH proteins of the different steps that eventually lead to the myogenic phenotype; b) the role of p300 and PCAF in this process; c) the interaction between Twist and Msx proteins; and d) a search for the existence and role of muscle restricted partners of p300, P/CAF and Twist. The isolation of co-regulators of muscle regulatory genes and understanding the roles of these molecules will be valuable toward our eventual goal, the development of preventive and therapeutic approaches to early diagnosis and intervention of craniofacial malformation and dygenesis.

要测试的总体假设是，通过干扰所需的转录核心调节剂，尤其是p300和/或PCAF，以及与其他早期肌生成分化的调节剂（例如MSX）相互作用，扭曲参与了肌发生的负调控。该假设将通过分子遗传以及对小鼠扭曲影响转录激活的机制的生化分析来检验，MEF2和BHLH蛋白的不同步骤最终导致了肌源性表型。 b）P300和PCAF在此过程中的作用； c）扭曲和MSX蛋白之间的相互作用； d）搜索p300，p/caf和Twist的肌肉受限伴侣的存在和作用。肌肉调节基因的共同调节因子的分离和理解这些分子的作用将对我们的最终目标，预防和治疗方法的发展和治疗方法的早期诊断和颅面畸形和二氧化作用有价值。