Mechanism of Imprinting in Drosophila

描述（由申请人提供）：这项工作的长期目标是利用模式生物——黑腹果蝇（Drosophila melanogaster）研究基因组印迹的遗传控制。基因组印记已被证明是果蝇Y染色体的一个普遍特性。通常，父系印记导致y连锁报告基因的抑制，而母系印记则使这些基因的表达相对较高。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，以了解它们在产生印记中的作用。我们还将对在印迹中发挥作用的基因进行全基因组筛选，并对印迹的定量或定性修饰因子进行筛选。我们将研究位于X染色体异染色质上的报告基因对印记的反应，以确定印记是Y染色体现象还是性染色体现象。最后，我们将开展一系列旨在阐明果蝇印迹的生物学原理的实验。具体来说，将测试三个假设：父亲印记是Y生育因子正确表达所必需的；印迹是一种沉默Y染色体上的转座子负载的机制；印记是一种控制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进化产生影响。

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.