Mechanism of Imprinting in Drosophila

描述（由申请人提供）：这项工作的长期目标是使用模式生物，黑腹果蝇，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染色体的一个普遍属性。典型地，父系印记导致Y连锁报告基因的抑制，而母系印记给出这些基因的相对高的表达。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亲本特异性印记的候选者。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。我们还将进行全基因组筛选，以筛选在印记中起作用的基因，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，我们将进行一系列旨在阐明果蝇中印记的生物学原理的实验。具体而言，将测试三个假设：父印迹是需要适当表达的Y生育因子;印迹是一种沉默转座子负载的Y染色体的机制;和，印迹是一种机制，用于控制rDNA的表达。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一般进化产生影响。

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.