DNA sequence and conformation directed positioning of nucleosomes by chromatin remodelers

真核生物的DNA被其组织压缩成染色质的几千倍。然而，与此同时，染色质在时间和空间上是透明的，允许进入DNA进行转录、复制、修复和重组。近年来，人们发现了许多染色质重塑复合体，并阐明了它们在DNA上重新定位核小体的机制。它们的ATP偶联活性以一种高度动态的方式改变染色质结构，以便蛋白质因子可以根据需要与DNA相互作用。有趣的是，细胞中含有数百种不同的染色质重塑复合体。它们的高数量和丰度表明，除了保持核小体的活力外，它们还具有其他功能。我们的准备工作表明，这些复合物是不同的，因为它们建立了重塑特异性的染色质结构。在这里，它被提议检查单个重塑复合体的位置核小体在DNA上的不同位置。我们打算鉴定位点特异性信号，这些信号被个体染色质重塑酶不同地识别和解释。这种复杂的特异性活性与体内高度相关，因为它允许它在相同的基因组位点上建立不同的染色质结构，从而调节DNA的可及性，并确定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 struc-ture in a highly dynamic manner so that protein factors can interact with the DNA as needed. Interest-ingly, the cell harbours hundreds of different chromatin remodeling complexes. Their high number and abundance suggests that they fullfill additional functions, next to keeping nucleosomes dynamic. Our preparatory 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 it allows it to establish distinct chromatin structures at the same genomic loci so that the accessibility of DNA is regulated and 'on' or 'off states of DNA dependent processes are determined.