Nukleosomen Positionierung durch Chromatin Remodeling Komplexe: Existenz und molekulare Grundlagen eines "Remodeler Codes"

染色质重塑复合物的核小体定位：“重塑代码”的存在和分子基础

• 批准号: 75998799
• 负责人: Professor Dr. Gernot M. Längst
• 金额: --
• 依托单位: Lehrstuhl für Biochemie III
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/75998799?language=en
• 关键词: Nukleosomen; Positionierung; durch; Chromatin; Remodeling

Eukaryotic DNA is compacted several thousand fold by its organization into chromatin. At the same time, however, chromatin is transparent in a temporally and spatially defined manner to allow access to the DNA for transcription, replication, repair and recombination. Recent years have witnessed the discovery of numerous chromatin remodeling complexes and the elucidation of the mechanisms by which they reposition nucleosomes on the DNA. Their ATP coupled activities alter the chromatin structure in a highly dynamic manner so that protein factors can interact with the DNA as needed. Interestingly, the cell harbours hundreds of different chromatin remodeling complexes. Their high number and abundance suggests that they fulfil additional functions, next to keeping nucleosomes dynamic. Our work indicates that the complexes are distinct in that they establish remodeler-specific chromatin structures. Here it is proposed to examine individual remodeling complexes that position nucleosomes to different places on the DNA. We intend to identify the locus specific signals that are recognized and interpreted differently by the individual chromatin remodeling enzymes. This complex specific activity is highly relevant in vivo as we have shown for the rRNA gene locus. The Nucleolar remodeling complex (NoRC) regulates transcription and the epigenetic state of the ribosomal genes by changing local chromatin structures. We will address the signals and molecular mechanisms that guide NoRC and other remodeling complexes in establishing specific chromatin structures, as those machines may define the ‘on’ or ‘off’ state of DNA dependent processes.

真核DNA通过组织成染色质而被压缩数千倍。然而，与此同时，染色质以时间和空间限定的方式是透明的，以允许接近DNA进行转录、复制、修复和重组。近年来发现了许多染色质重塑复合物，并阐明了它们在DNA上重新定位核小体的机制。它们的ATP偶联活性以高度动态的方式改变染色质结构，使得蛋白质因子可以根据需要与DNA相互作用。有趣的是，该细胞含有数百种不同的染色质重塑复合物。它们的高数量和丰度表明它们除了保持核小体的动态外，还具有其他功能。我们的工作表明，复合物是不同的，因为它们建立重塑特异性染色质结构。在这里，它建议检查个人的重塑复合物，定位核小体的DNA上的不同地方。我们的目的是确定基因座特异性的信号，识别和解释不同的个别染色质重塑酶。这种复合物的特异性活性在体内是高度相关的，正如我们对rRNA基因座所显示的那样。核仁重塑复合物（NoRC）通过改变局部染色质结构来调节核糖体基因的转录和表观遗传状态。我们将讨论指导NoRC和其他重塑复合物建立特定染色质结构的信号和分子机制，因为这些机器可以定义DNA依赖过程的“开”或“关”状态。