Mechanism of Imprinting in Drosophila

果蝇印记机制

• 批准号: 7260495
• 负责人: KENT G GOLIC
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260495
• 关键词: Animal Model; Biological; Biological Process; Candidate Disease Gene; Chromatin Structure; Chromosomes; DNA Methylation; Drosophila genus; Drosophila melanogaster; Evolution; F Factor; Fertility; Genes; Genetic; Genome; Genomic Imprinting; Goals; Hereditary Disease; Heterochromatin; Histone Acetylation; Histones; Human; Link; Methylation; Modeling; Mutation; Parents; Play; Principal Investigator; Process; Property; Range; Recombinant DNA; Reporter; Reporter Genes; Repression; Ribosomal DNA; Role; Screening procedure; Sex Chromosomes; Surveys; Testing; Transgenes; Work; X Chromosome; Y Chromosome; imprint; male; maternal imprint; paternal imprint; programs; research study; response

DESCRIPTION (provided by applicant): The long-term goal of this work is to use the model organism, Drosophila melanogaster, to investigate the genetic control of genomic imprinting. Genomic imprinting has been shown to be a general property of the Drosophila Y chromosome. Typically, a paternal imprint leads to repression of Y-linked reporter genes, while a maternal imprint gives relatively high expression of those genes. DNA methylation, histone methylation, histone acetylation, and chromatin structure are all candidates for generating a parent-specific imprint. We will investigate candidate genes that are known to be involved in these processes for their role in generating an imprint. We will also undertake a genome wide screen for genes that play a role in imprinting with a screen for quantitative or qualitative modifiers of the imprint. We will investigate reporter transgenes located in X chromosome heterochromatin for response to an imprint to determine whether imprinting is a Y chromosome phenomenon or a sex chromosome phenomenon. Finally, we will carry out sets of experiments aimed at elucidating the biological rationale for imprinting in Drosophila. Specifically, three hypotheses will be tested: that paternal imprinting is needed for proper expression of the Y fertility factors; that imprinting is a mechanism for silencing the transposon load carried by the Y chromosome; and, that imprinting is a mechanism for controlling expression of the rDNA. The results of these experiments will have implications for understanding human genetic disorders arising out of imprinting, and for the evolution of imprinting in general.

描述（由申请人提供）：这项工作的长期目标是利用模式生物果蝇（Drosophila melanogaster）来研究基因组印记的遗传控制。基因组印记已被证明是果蝇 Y 染色体的一般特性。通常，父本印记会导致 Y 连锁报告基因的抑制，而母本印记会导致这些基因相对较高的表达。 DNA 甲基化、组蛋白甲基化、组蛋白乙酰化和染色质结构都是生成亲本特异性印记的候选因素。我们将研究已知参与这些过程的候选基因在产生印记中的作用。我们还将对在印记中发挥作用的基因进行全基因组筛选，并筛选印记的定量或定性修饰剂。我们将研究位于 X 染色体异染色质中的报告基因转基因对印记的反应，以确定印记是 Y 染色体现象还是性染色体现象。最后，我们将进行一系列实验，旨在阐明果蝇印记的生物学原理。具体而言，将测试三个假设：Y 生育因子的正确表达需要父系印记；印记是一种沉默 Y 染色体携带的转座子负载的机制；并且，该印记是控制 rDNA 表达的机制。这些实验的结果将对理解由印记引起的人类遗传疾病以及印记的总体进化产生影响。