One of the persistent enigmas of gene regulation is how the chromatin organisation, which reliably packages eukaryotic DNA, can at the same time be transparent to allow access of regulatory factors. Recent years have witnessed the discovery of enzymes modifying the structure of chromatin in response to cell-internal and -external cues, rendering chromatin a highly dynamic structure. Chromatin remodeling enzymes couple ATP hydrolysis to alterations of the chromatin structure at the level of the nucleosomal-array. Post-translational modifications of the histone tails are correlated with distinct chromatin states and DNA accessibility. The recent advances in proteomic analyses revealed novel modifications in the nucleosome core, many of which are positioned at the histone-DNA interface. Little is known about the role of these modifications, but several modifications are implicated to modulate chromatin remodeling, suggesting an intimate link between histone modifications and nucleosome remodelers in modulating chromatin dynamics. However, detailed analysis and functional testing is still lacking. (i) I propose an in vivo screen, to identify histone modifications and their combinations that modulate chromatin dynamics. (ii) We want to address the mechanistical basis of chromatin dynamics. Do ATP-dependent remodeler generate accessible DNA by constantly moving nucleosomes or are they regulated complexes that required additional signals that lead to localized nucleosome remodeling? (iii) Do remodeling complexes work similarly well in different higher order structures of chromatin? Or are specialized complexes required for different compaction states of chromatin?
