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

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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.