Figure 8.

A model of the two-step activation of Eomes locus during specification of definitive endoderm from ES cells, conserved between human and mouse. Eomes is poised in embryonic stem cells, marked by H3K4me3 and H3K27me3. During initial differentiation, Tbx3 associates with histone demethylase Jmjd3 and activates the Eomes enhancer, promoting enhancer–promoter interaction. This spatial reorganization of the chromatin primes the cells to respond to Activin A signalling, by allowing Eomes to promote Jmjd3-mediated transcriptional activation of the Eomes itself as well as the core regulators of endoderm.