Mouse embryonic stem cells (mESCs) represent an exceptional model for understanding how transcriptional responses are regulated by signalling pathways during development. Treatment with a cocktail of MEK and GSK3β inhibitors ("2i") induces ground state pluripotency, characterized by increased self-renewal, reduced DNA methylation, and uniformly high expression of pluripotency markers. Polycomb Repressive Complex 2 (PRC2) is a key developmental regulator controlling stem cell self-renewal and differentiation decisions, and altered expression of PRC2 target genes is a signature of 2i-mediated ground state conversion.
View Article and Find Full Text PDFMulticellular organisms arise from a single genome template in the zygote, necessitating the cells of the developing embryo to up- and downregulate specific genes to establish and maintain their identity. This template is maintained, propagated, and interpreted as chromatin, a polymer of nucleic acids and associated structural and regulatory proteins. Recent genome-wide surveys documented a wealth of disease-associated mutations in chromatin factors, indicating their fundamental significance and potential for therapeutic targeting.
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