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使用模型有机体，即果蝇Melanogaster，研究基因组印迹的遗传控制。基因组印迹已被证明是果蝇染色体的一般特性。通常，父亲的烙印会导致抑制Y连锁的报告基因，而母体烙印给出了这些基因的相对较高的表达。 DNA甲基化，组蛋白甲基化，组蛋白乙酰化和染色质结构都是产生母体特异性烙印的候选者。我们将研究候选基因，这些基因在这些过程中涉及这些过程，因为它们在产生烙印中的作用。我们还将对基因进行基因组宽屏幕，这些屏幕在印刷屏幕上发挥作用，以构成烙印的定量或定性修饰符。我们将调查位于X染色体异染色质中的记者转基因，以响应烙印，以确定印记是y染色体现象还是性染色体现象。最后，我们将进行旨在阐明果蝇印记的生物学原理的实验集。具体而言，将检验三个假设：正确表达Y生育因素需要父亲印迹；这种烙印是使Y染色体携带的转座子负荷沉默的机制。而且，这种烙印是控制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一般印迹的演变产生影响。