Heterochromatin remodeling in embryonic stem cells proceeds through stochastic de-stabilization of regional steady-states

Publication date: Available online 20 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Anastasia Christogianni, Eleftheria Chatzantonaki, Katerina Soupsana, Ioannis Giannios, Aggeliki Platania, Anastasia S. Politou, Spyros Georgatos
Cell differentiation is associated with progressive immobilization of chromatin proteins, expansion of heterochromatin, decrease of global transcriptional activity and induction of lineage-specific genes. However, how these processes relate to one another remains unknown. We show here that the heterochromatic domains of mouse embryonic stem cells (ESCs) are dynamically distinct and posesses a mosaic sub-structure. Although random spatio-temporal fluctuations reshuffle continously the chromatin landscape, each heterochromatic territory maintains its dynamic profile, exhibiting robustness and resembling a quasi-steady state. Transitions towards less dynamic states are detected sporadically as ESCs downregulate Nanog and exit the self-renewal phase. These transistions increase in frequency after lineage-commitment, but evolve differently depending on cellular context and transcriptional status. We propose that chromatin remodeling is a step-wise process, which involves stochastic de-stabilization of regional steady states and formation of new dynamic ensembles in coordination to changes in the gene expression program.



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