Transcriptional regulatory complexes associated with cardiac hypertrophy

与心脏肥大相关的转录调节复合物

• 批准号: nhmrc : 367643
• 负责人: A/Pr Xiao-Jun Du
• 金额: $ 31.64万
• 依托单位: Baker IDI Heart and Diabetes Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/transcriptional-regulatory-complexes-cardiac-hypertrophy/77320
• 关键词: Transcriptional; regulatory; complexes; associated; cardiac

Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression. It has been well known that a group of genes are altered (up or down) in the heart under conditions such as heart muscle overgrowth (ie hypertrophy), aging or of abnormal beating function. The reasons for such altered gene activity remain poorly understood. Although recent studies from research on genetics or cancer have revealed the important role of the DNA and DNA-bound proteins (called histone) in the control of gene activity, this has rarely been studied in the heart. In this project, we will test our hypothesis that DNA-histone structure is a key factor that control gene activities in ageing and diseased heart. This proposal is supported by our recent findings showing that in the hypertrophied heart, such DNA-histone structure did alter in such a way that fits well with alterations in gene activity. We have planned a series of studies to test this hypothesis in a systematic fashion. A number of sophisticated and cutting-edge techniques and experimental models of heart hypertrophy will be used. We will analyse changes in activities of a number of selected genes in the heart and also analyse changes in DNA-histone structures and chemical modifications at particular regions. These changes will then be linked together. We will also explore the possibility of modulating DNA-histone structure, thereby controlling the degree of cardiac hypertrophy. This project is the joint efforts of scientists with substantial experience in research on gene activity and heart diseases, and is highly likely to generate novel information to and hold significant therapeutic potential.

随着人类基因组（即DNA序列）的成功解码，一项主要任务是了解基因的活性如何导致相应蛋白质的变化。由于蛋白质是细胞结构和功能的重要组成部分，因此蛋白质数量和质量的变化将对疾病的发生和发展起关键作用。众所周知，在心肌过度生长（即肥大）、衰老或跳动功能异常的情况下，心脏中的一组基因发生改变（向上或向下）。这种基因活性改变的原因仍然知之甚少。尽管最近的遗传学或癌症研究揭示了DNA和DNA结合蛋白（称为组蛋白）在控制基因活性中的重要作用，但很少在心脏中进行研究。在这个项目中，我们将验证我们的假设，即DNA-组蛋白结构是一个关键因素，控制基因的活动，在老化和患病的心脏。我们最近的发现支持了这一建议，这些发现表明，在肥大的心脏中，这种DNA-组蛋白结构确实以与基因活性变化很好地吻合的方式发生了变化。我们已经计划了一系列的研究来系统地检验这一假设。将使用一些复杂和尖端的技术和心脏肥大的实验模型。我们将分析心脏中一些选定基因的活性变化，并分析特定区域的DNA组蛋白结构和化学修饰的变化。这些变化将联系在一起。我们还将探索调节DNA-组蛋白结构的可能性，从而控制心脏肥大的程度。该项目是在基因活性和心脏病研究方面具有丰富经验的科学家的共同努力，极有可能产生新的信息，并具有重要的治疗潜力。