DNA sequence and conformation directed positioning of nucleosomes by chromatin remodelers

染色质重塑剂对核小体的 DNA 序列和构象定向定位

• 批准号: 35450097
• 负责人: Professor Dr. Gernot M. Längst
• 金额: --
• 依托单位: Abteilung Chromatin-Netzwerke
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35450097?language=en
• 关键词: DNA; sequence; conformation; directed; positioning

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.

真核 DNA 通过组织成染色质而被压缩数千倍。然而，与此同时，染色质在时间和空间上是透明的，允许接触 DNA 进行转录、复制、修复和重组。近年来，人们发现了大量染色质重塑复合物，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，以便蛋白质因子可以根据需要与 DNA 相互作用。有趣的是，细胞含有数百种不同的染色质重塑复合物。它们的数量和丰度高表明它们除了保持核小体动态之外还具有其他功能。我们的准备工作表明，这些复合物的独特之处在于它们建立了重塑者特异性染色质结构。这里建议检查将核小体定位到 DNA 上不同位置的个体重塑复合物。我们打算识别被各个染色质重塑酶以不同方式识别和解释的位点特异性信号。这种复杂的特异性活性在体内高度相关，因为它允许在相同的基因组位点建立不同的染色质结构，从而调节 DNA 的可及性并确定 DNA 依赖性过程的“开”或“关”状态。