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

Research paper by Anastasia A Christogianni, Eleftheria E Chatzantonaki, Katerina K Soupsana, Ioannis I Giannios, Aggeliki A Platania, Anastasia S AS Politou, Spyros S Georgatos

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Biochimica et biophysica acta



Abstract

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.