Investigating Mechanisms by which Tandem Repeats Mediate b1 Paramutation

研究串联重复介导 b1 副突变的机制

• 批准号: 0235329
• 负责人: Vicki Chandler
• 金额: $ 73.2万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2008-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0235329&HistoricalAwards=false
• 关键词: Investigating; Mechanisms; Tandem; Repeats; Mediate

The control of where and when genes are expressed is fundamental to the development and function of all organisms. Genes are within DNA molecules that are packaged into chromosomes. How the genes are packaged, referred to as chromatin organization, and the activities of protein complexes that modulate chromatin organization, such as chromatin remodelling complexes, are crucial for correct gene regulation. Inappropriate activation or inactivation of genes affects growth, development and physiology, which impacts clinical medicine and agriculture. This project's experiments investigate chromatin-level gene interactions in maize (corn). Maize is an excellent model system, in that the genetic tools available allow experiments not possible in humans or most animals. Unlike certain model genetic systems such as yeast and fruit flies, maize has gene and chromosome organization similar to humans and other mammals. We study the regulated expression of the genes required for the synthesis of the purple anthocyanin pigments in maize. Changes in purple gene activity produce obvious visual changes in pigment, easily revealing gene activity and inactivity, providing a powerful system for experimentation. In particular this project studies paramutation, which occurs when two different forms of the same gene interact, and this interaction leads to a reduction in expression of one gene. This change in expression is passed on to progeny, resulting in altered gene expression in subsequent generations. With prior NSF funding this project completed a series of experiments that identified what regions of the gene are required for this phenomenon to occur and isolated a series of mutations in other genes that perturb this phenomenon. In addition, previous experiments demonstrated that paramutation is associated with specific chromatin changes that are transmitted to progeny. The experiments currently being pursued are designed to further characterize the DNA sequences required for paramutation and to test specific models for how distinct chromatin states are established, maintained and transmitted to progeny. As genetic mechanisms are frequently conserved between organisms, results from the experiments with maize will provide important paradigms for many species, such as mammals and other important plants, where genetic tools are not as well developed.

基因何时何地表达的控制对所有生物体的发育和功能都是至关重要的。基因存在于DNA分子中，DNA分子被包装成染色体。基因是如何包装的，称为染色质组织，以及调节染色质组织的蛋白质复合体的活动，如染色质重塑复合体，对于正确的基因调控至关重要。基因的不适当激活或失活会影响生长、发育和生理，从而影响临床医学和农业。该项目的实验研究了玉米(玉米)中染色质水平的基因相互作用。玉米是一个很好的模型系统，因为可用的遗传工具允许进行在人类或大多数动物上不可能进行的实验。与酵母和果蝇等某些模式遗传系统不同，玉米的基因和染色体组织类似于人类和其他哺乳动物。我们研究了玉米合成紫色花青素所需基因的调控表达。紫色基因活性的变化会在色素中产生明显的视觉变化，很容易揭示基因的活性和不活性，为实验提供了一个强大的系统。特别是，这个项目研究了当同一基因的两种不同形式相互作用时发生的顺变，这种相互作用导致一个基因的表达减少。这种表达的变化会传递给后代，导致后代的基因表达发生变化。在NSF之前的资助下，该项目完成了一系列实验，确定了这种现象发生所需的基因区域，并分离出了扰乱这种现象的其他基因的一系列突变。此外，以前的实验证明，参数突变与传递给后代的特定染色质变化有关。目前正在进行的实验旨在进一步确定参变所需的DNA序列的特征，并测试如何建立、维持和传递给后代的不同染色质状态的特定模型。由于遗传机制在生物体之间往往是保守的，玉米实验的结果将为许多物种提供重要的范例，如哺乳动物和其他重要植物，这些物种的遗传工具还不够发达。