8th Annual Symposium
Physics of Cancer
October 4-6, 2017
|PoC - Physics of Cancer - Annual Symposium|
Establishing nuclear subcompartments and chromatin patterns to regulate gene expression
German Cancer Research Center (DKFZ) and Bioquant, Division of Chromatin Networks, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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The cell nucleus lacks internal membrane boundaries and soluble protein factors are rapidly distributed on the 10 µm length scale by free diffusive transport within seconds. Nevertheless, the cell establishes specific patterns of active and silenced genes. The underlying chromatin states are characterized by a distinct composition of chromosomal proteins and RNA, patterns of histone modifications and DNA methylation marks as well as structural features like the position and density of nucleosomes and the 3D folding of the nucleosome chain. To understand the interplay between these features, we investigate the mobility and chromatin interactions of protein factors to dissect the formation of transcriptional active or repressive nuclear subcompartments by a combination of fluorescent microscopy methods in living cells. Based on these measurements biophysical models are derived that address the following questions: (i) How do chromatin modifying enzymes and transcription factors translocate in the nucleus to find their target loci? (ii) What mechanisms drive the assembly of chromatin subcompartments like pericentric heterochromatin? (iii) How is the induction of gene expression coupled to the chromatin state?