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

真核生物的DNA通过其组织紧凑成染色质几千倍。然而，与此同时，染色质在时间和空间上是透明的，从而允许进入DNA进行转录、复制、修复和重组。近年来，人们发现了大量的染色质重塑复合体，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体。它们的数量和丰度表明，它们除了保持核小体的动态外，还发挥了额外的功能。我们的工作表明，这些复合体是不同的，因为它们建立了重构体特有的染色质结构。在这里，建议检查单个重塑复合体，这些重塑复合体将核小体定位到DNA上的不同位置。我们打算确定由各个染色质重塑酶识别和解释不同的基因座特定信号。正如我们对rRNA基因座所显示的那样，这种复杂的特定活性在体内具有高度相关性。核仁重塑复合体(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和其他重塑复合体建立特定染色质结构的信号和分子机制，因为这些机器可能定义DNA依赖过程的“开”或“关”状态。

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.