Genomic imprinting in Drosophila

果蝇的基因组印记

• 批准号: 216857-2010
• 负责人: Lloyd, Vett
• 金额: $ 2.91万
• 依托单位: Mount Allison University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546458
• 关键词: Genomic; imprinting; Drosophila

Genomic imprinting, the epigenetic marking of the genomes according to their parental origin, has been documented in a wide variety of animals and plants including mammals, higher and lower vascular plants, fish and insects. Among the latter is the model organism Drosophila melanogaster. During the tenure of my last two NSERC discovery grants my research group identified genes that regulate imprinting. These genes fall into different classes: those acting in the somatic cells maintain the imprint and those acting in the germ-line erase and then re-set the imprint from previous generations. Among the genes we identified were a number of highly conserved chromatin proteins that modify histones or form higher order chromatin structures, some of these have recently been found to play a role in mammalian imprinting. In this application, I propose to identify the last, and most intractable, class of imprint regulatory genes - those that erase the imprint. I also propose to extend our initial work investigating the evolutionary conservation of imprinting by looking for evidence of imprinting in previously un-investigated non-model organisms. The correct imprinting of early acting genes is vital for normal human development, and as a result a number of diseases arise from defective imprinting. Likewise, disrupted imprinting contributes to the poor viability of cloned animals and animals generated through assisted reproductive technology. As is true in mammals, Drosophila imprints its genome, however, in only non-essential genes are imprinted so that the imprinting process can be more readily genetically manipulated. Coupled with sophisticated genetic tools, this makes Drosophila a good model system in which to identify the molecular mechanism of imprinting.

基因组印记是指基因组根据其亲本来源进行的表观遗传标记，已在包括哺乳动物、高等和低等维管植物、鱼类和昆虫在内的多种动物和植物中被证实。在后者中有模式生物黑腹果蝇（Drosophila melanogaster）。在我的最后两个NSERC发现奖的任期内赠款我的研究小组确定了调节印记的基因。这些基因分为不同的类别：那些在体细胞中起作用的基因保持了印记，而那些在生殖细胞中起作用的基因消除了前几代的印记，然后重新设置。在我们鉴定的基因中，有许多高度保守的染色质蛋白，它们修饰组蛋白或形成更高级的染色质结构，其中一些最近被发现在哺乳动物印迹中发挥作用。在这个应用程序中，我建议确定最后，也是最棘手的一类印记调控基因-那些消除印记的基因。我还建议延长我们的初步工作调查的印记的进化保护，通过寻找以前未调查的非模式生物的印记的证据。早期作用基因的正确印记对人类的正常发育至关重要，因此许多疾病都是由印记缺陷引起的。同样，破坏印迹有助于克隆动物和通过辅助生殖技术产生的动物的生存能力差。 与哺乳动物一样，果蝇也会在基因组上留下印记，但只有非必需基因会被印记，因此印记过程更容易被基因操纵。再加上复杂的遗传工具，这使得果蝇成为一个很好的模型系统，在其中确定印迹的分子机制。