Chromatin organization and behavior in RAS-transformed mouse fibroblasts

In higher eukaryotic cells, a string of nucleosomes, where long genomic DNA is wrapped around core histones, are rather irregularly folded into a number of condensed chromatin domains, which have been revealed by super-resolution imaging and Hi-C technologies. Inside the domains, nucleosomes fluctuate and locally behave like a liquid. The behavior of chromatin could be highly related to DNA transaction activities such as transcription and repair, and cancer cells often upregulate such activities. We investigated oncogenic-HRAS (Gly12Val)-transformed mouse fibroblasts CIRAS-3 cells, which are tumorigenic and highly metastatic, and their parental 10T1/2 cells. Their Hi-C analysis revealed enriched interactions of B-B compartment, which likely represents transcriptionally inactive chromatin, in CIRAS-3 cells, suggesting that CIRAS-3 cells increased heterochromatin regions. Since it is known that condensed chromatin works as a spring that resists nuclear deformation, our findings suggest that the more constrained chromatin in transformed cells could benefit the cancer metastasis process with nuclear deformation.