Model depicting the proposed dynamic TF binding and epigenetic hierarchy that governs establishment of FOXA1-dependent enhancers. FOXA1 collaborates with additional pioneer factors (e.g., GATA family factors) to trigger transcriptional competency of specific enhancers. We propose that this involves the initiation of an epigenetic switch consisting of DNA demethylation and induction of H3K4 methylation. These epigenetic changes allow for subsequent recruitment of transcriptional regulatory effectors, among which are nuclear receptors (NR) that directly regulate gene expression in response to environmental cues. See the Discussion section for further details.
