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The role of heterochromatin enzymes on the biology of their targets

Final Report Summary - PICHV2.0 (The role of heterochromatin enzymes on the biology of their targets)

During the course of the PICh v2.0 project, the major aims were to understand the biological features of three critical heterochromatic regions of the mammalian genome, both in development and in disease. We focused our attention on telomeres in cancer, on pericentromeres during development and on the ribosomal RNA locus. We have identified a novel pathway of telomere driven genome instability in cancer that we named Targeted Telomere Insertions and that involves an aberrant recombination of telomeres to interstitial genomic regions. We have identified in an unbiased manner, the function of important heterochromatin enzymes such as DNA methyltransferases and SUV39H1/2 at their major target: the pericentromeric locus. Finally we have developped end-targeting PICh and established a set of rules to design efficient locus specific chromatin capture assays.