MOLECULAR GENETICS OF DOSAGE COMPENSATION IN DROSOPHILA

描述（来自应用程序的逐字）：剂量补偿是一个惊人的 基因特异性调控和染色体之间相互作用的例子 架构这个过程已经进化到使X连锁基因表达 男性有一条X染色体，女性有两条。 物种 在分子水平上检查，剂量补偿是由 修饰X染色体以调节染色质的性别特异性因子 结构和基因表达。 在果蝇中，剂量补偿是可以实现的， 至少部分地通过位点特异性组蛋白H4乙酰化， 雄性特异性、X特异性蛋白复合物（由MSL蛋白组成，和 可能是非编码roX RNA）。 我们在下一个资助期的重点是 理解果蝇剂量的精确的X染色体特异性 补偿复合体 我们的实验将测试一种新的识别X连锁基因的模型， MSL综合体 我们最近获得的证据表明，在野生型男性， MSL复合物在~30个染色质进入位点形成，仅沿沿着分布 然后顺式吸引到可能是共同的序列或蛋白质上， 基因组中的活跃基因。 这代表着一个重大的变化 从长期以来的预期，大多数X连锁基因将有 X特异性增强子样靶序列被MSL复合物识别， 我们的模型提出了有趣的相似之处与哺乳动物的剂量 赔偿 在果蝇和人类中，调节分子通常 限制在X染色体的顺式，但如果带到常染色体，可以传播 在剂量补偿之前从未对基因产生影响。 剖析潜在的机制 这些表观遗传调控过程将提供对许多重要的 生物学问题，包括人类的正常和疾病状态。 的高超 多线染色体的空间分辨率，一个确定的起始位点， 传播，以及蛋白质和RNA传播中突变体的可用性 组件使MSL复杂的一个理想的模型系统，以确定如何改变 染色质结构影响复杂生物体中的基因表达。

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.