The function of dSU(VAR)3-9 in heterochromatin spreading and establishment

dSU(VAR)3-9在异染色质扩散和建立中的功能

• 批准号: 5368865
• 负责人: Professor Dr. Axel Imhof
• 金额: --
• 依托单位: Forschungsbereich Physiologische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5368865?language=en
• 关键词: function; dSU; VAR; heterochromatin; spreading

The molecular basis of several epigenetic phenomena is thought to depend on the chromatin structure of the studied gene. One of the most intriguing observations in this regard is the position effect in which a certain-mostly repressive-chromatin structure can dramatically affect the expression of neighbouring genes. While this effect has been intensively studied over the last decades, its molecular basis remains unclear. In the last two years it has become clear that modifications of histones play an important role in the establishment and maintenance of certain chromatin structures. It is therefore a very likely hypothesis that histone modifications are also involved in the process mentioned above. In this study we plan to address directly the question whether a particular histone modification, namely histone methylation, is involved in the apparent "spreading" effect and whether we can observe a physically spreading of methylation and chromatin associated proteins along the chromosome. To do this we will perform chromatin immunoprecipitation experiment with chromatin prepared from various mutant flies and tissue culture cells using antibodies against known heterochromatin associated proteins and modified histones. In a parallel approach we will attempt to reconstruct some of the aspects of heterochromatin in the test tube. We will then monitor spreading effects in order to define the minimal requirements for heterochromatin spreading in vitro.

几种表观遗传现象的分子基础被认为取决于所研究基因的染色质结构。在这方面，最有趣的观察之一是位置效应，其中某个主要是抑制性的染色质结构可以显着影响相邻基因的表达。虽然这种效应在过去几十年中得到了深入研究，但其分子基础仍然不清楚。在过去的两年中，组蛋白的修饰在某些染色质结构的建立和维持中起着重要的作用已经变得清楚。因此，这是一个非常可能的假设，即组蛋白修饰也参与了上述过程。在这项研究中，我们计划直接解决的问题，是否一个特定的组蛋白修饰，即组蛋白甲基化，参与了明显的“扩散”效应，以及我们是否可以观察到一个物理扩散的甲基化和染色质相关蛋白沿着染色体。为此，我们将使用已知异染色质相关蛋白和修饰组蛋白的抗体，对从各种突变果蝇和组织培养细胞制备的染色质进行染色质免疫沉淀实验。在一个平行的方法中，我们将尝试在试管中重建异染色质的某些方面。然后，我们将监测扩散效应，以确定异染色质体外扩散的最低要求。