Chromatin Dynamics in Development and Disease

ended

The cell nucleus is organized and compartmentalized into a highly ordered structure that contains DNA, RNA, chromosomal and histone proteins which make up a structure called chromatin. The dynamics associated with these various components are responsible for regulating physiological processes and the overall stability of the genome. The destabilization of such regulatory mechanisms that act on the chromatin structure are implicated in pathologies such as cancer. Higher order organization of chromatin results in chromosomes which occupy discrete territories within the cell nucleus. Most nuclear processes occur or at least being initiated onto the chromosomes which makes them the main organizing factors in the nucleus. Several proteins that are involved in the replication of DNA, gene transcription and the processing of RNA are found enriched in discrete focal structures. An emerging question is how these structures assemble and are maintained in the absence of membranes and moreover what are the kinetics of stable binding and/or rapid exchange of their components. The dynamic assembly and modification of chromatin during developmental processes as well as the deregulation of such chromatin dynamics during the onset of disease lacks mechanistic insights at present. To address these questions we have put forward a multidisciplinary approach which involves molecular, cellular and systems level approaches by assembling a group of scientists from academia and industry with cross disciplinary expertise and capabilities.