title: Heterochromatin remodeling in embryonic stem cells proceeds through stochastic de-stabilization of regional steady-states.
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 possesses a mosaic sub-structure. Although random spatio-temporal fluctuations reshuffle continuously 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 transitions 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.
authors.affiliation: The Laboratory of Biology, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Christogianni
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biology, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Chatzantonaki
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biological Chemistry, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Soupsana
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biology, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giannios
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biology, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Platania
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biological Chemistry, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Politou
authors.affiliation: Stem Cell and Chromatin Group, The Institute of Molecular Biology and Biotechnology, Biomedical Division, FORTH-ITE, Greece; The Laboratory of Biology, The University of Ioannina, Faculty of Medicine, 45 110 Ioannina, Greece. Electronic address: sgeorgat@cc.uoi.gr.
authors.forename: Spyros
authors.initials: S
authors.lastname: Georgatos
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse
keywords: Chromatin remodeling; Frap; Heterochromatin; Heterochromatin protein 1; Protein dynamics; Stem cells