Model depicting the epigenetic mechanisms regulating cell state transitions. Proliferating (PC) and hypertrophic chondrocytes (HC) were isolated from embryonic limbs using flow cytometry for ChIP-seq and laser-microdissection for RNA-seq. Prehypertrophic chondrocytes (PHC) were included in different cell populations. Comparison of the epigenetic pattern between cell types indicates that gene repression in HC is initiated by the gain of H3K27me3 at promoters still decorated with declining levels of activating marks. Cell type–specific enhancers show a rapid adaption of H3K27ac peaks to differential gene expression. Whereas PC-specific enhancers are associated with chondrogenic genes, HC-specific enhancers regulate metabolic pathways. H3K4me3: light blue; H3K9ac : dark green; H3K27ac : light green; H3K36me3   : dark blue; H3K27me3  : red.