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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=477802
• 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.

基因组印迹是基因组的表观遗传标记，根据其亲代来源，已在包括哺乳动物、高等和低等维管束植物、鱼类和昆虫在内的各种动植物中得到证实。后者中有一种模式生物--黑腹果蝇。在我最后两次获得NSERC发现基金的任期内，我的研究小组识别出了调节印记的基因。这些基因分为不同的类别：那些作用于体细胞的基因保持印记，那些作用于生殖系的基因擦除，然后重新设定前几代的印记。在我们鉴定的基因中，有一些高度保守的染色质蛋白，它们可以修饰组蛋白或形成更高阶的染色质结构，其中一些基因最近被发现在哺乳动物的印记中发挥作用。在这一应用中，我建议识别最后一类也是最难处理的印记调控基因--那些消除印记的基因。我还建议通过在以前未被研究的非模式生物中寻找印记的证据，来扩展我们研究印记进化保守的初步工作。早期作用基因的正确印迹对人类的正常发育至关重要，因此许多疾病都是由印迹缺陷引起的。同样，被破坏的印记导致克隆动物和通过辅助生殖技术产生的动物的生存能力较差。就像哺乳动物一样，果蝇会印记它的基因组，然而，只有非必要的基因会印记，所以印记过程可以更容易地通过基因操作。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，在其中识别印记的分子机制。