MOLECULAR GENETICS OF DOSAGE COMPENSATION IN DROSOPHILA

果蝇剂量补偿的分子遗传学

• 批准号: 6636025
• 负责人: Mitzi I Kuroda
• 金额: $ 13.94万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6636025
• 关键词: Drosophilidae; chromatin; developmental genetics; gender difference; gene dosage; gene expression; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; nucleoproteins; regulatory gene; sex chromosomes; tissue /cell culture

DESCRIPTION (verbatim from the application): Dosage compensation is a striking example of the interplay between gene-specific regulation and chromosomal architecture. This process has evolved to make X-linked gene expression equivalent in males with one X chromosome and females with two. In species examined at the molecular level, dosage compensation is mediated by sex-specific factors that decorate the X chromosomes to regulate chromatin structure and gene expression. In Drosophila, dosage compensation is achieved, at least in part, through site-specific histone H4 acetylation, modulated by a male-specific, X-specific protein complex (composed of the MSL proteins, and possibly non-coding roX RNAs). Our focus in the coming grant period will be to understand the exquisite X chromosome-specificity of the Drosophila dosage compensation complex. Our experiments will test a new model for the recognition of X linked genes by the MSL complex. We recently obtained evidence that in wild type males, the MSL complex forms at ~30 chromatin entry sites, distributed exclusively along the X, and is then attracted in cis to sequences or proteins that may be common to active genes throughout the genome. This represents a significant change from the longstanding expectation that most X-linked genes would have X-specific, enhancer-like target sequences recognized by the MSL complex in trans. Our model raises interesting parallels with mammalian dosage compensation. In both flies and humans, regulatory molecules are normally restricted in cis to the X chromosome, but if brought to autosomes, can spread on genes never before dosage compensated. Dissecting the mechanisms underlying these epigenetic regulatory processes will provide insight into many important biological problems, including normal and disease states in humans. The superb spatial resolution of polytene chromosomes, a defined initiation site for spreading, and the availability of mutants in the protein and RNA spreading components make the MSL complex an ideal model system to determine how changes in chromatin architecture affect gene expression in complex organisms.

描述（逐字从应用程序中）：剂量补偿是一个引人注目的 基因特异性调节和染色体之间相互作用的示例 建筑学。这个过程已经演变成X连锁基因表达 在男性中等同于一个X染色体，有两个染色体。 在物种中 在分子水平上检查的剂量补偿是由 装饰X染色体以调节染色质的性别特异性因素 结构和基因表达。 在果蝇中，实现了剂量补偿， 至少部分地通过特异性组蛋白H4乙酰化，由A调制 男性特异性的X特异性蛋白质复合物（由MSL蛋白组成，和 可能是非编码ROX RNA）。 我们在即将到来的赠款期间的重点是 了解果蝇剂量的精美X染色体特异性 补偿复合物。 我们的实验将测试一个新模型，以通过 MSL复合物。 我们最近获得了证据，表明在野生型男性中 MSL复合物形式在〜30个染色质进入位点，仅分布 x，然后以顺式吸引到可能是常见的序列或蛋白质 整个基因组的活性基因。 这代表了一个重大变化 从长期以来的期望，大多数X连锁基因都会有 由MSL复合物在 反式。 我们的模型与哺乳动物剂量相似 赔偿。 在苍蝇和人类中，调节分子通常是 限制在X染色体上，但如果将常染色体带到常染色体，则可以传播 关于剂量从未补偿的基因。 解剖基础机制 这些表观遗传调节过程将为许多重要 生物学问题，包括人类的正常和疾病状态。 精湛的 多丹染色体的空间分辨率，这是一个定义的起始位点 扩散，以及蛋白质和RNA扩散中突变体的可用性 组件使MSL复合物成为确定如何变化的理想模型系统 在染色质结构中会影响复杂生物的基因表达。