Model for regulatory shift from HBE to ASE during epiblast maturation.

<p>(A) In the late preimplantation epiblast and in ES cells, pluripotency factors (mainly Oct4) and Nodal/Activin signaling activate HBE, which up-regulates <i>Nodal.</i> However, Nanog bound on HBE represses ASE so that expression levels of <i>Nodal</i> remain low. (B) In the postimplantation epiblast and in EpiSCs, changes in the combination of HBE-bound factors allow ASE to take over from HBE as the predominant enhancer driving <i>Nodal</i> expression, and the positive regulatory loop between <i>Nodal</i> and ASE is established, leading to higher expression levels.</p>