Developmental regulation of gene expression by transcriptional enhancers. (A) Enhancer and promoter sequences are compacted in chromatin prior to gene activity. Pioneer factors can interact with the locus, changing its accessibility for binding by activating TFs. (B) Partially or fully assembled sets of TFs can associate with the enhancer and the promoter. In cell types in which the enhancer is actively repressed, specific TFs may remodel chromatin structure to reduce but not eliminate access. Bifunctional TFs may be alternatively associated with corepressors or coactivators depending on the signaling state of the cell. (C) In the active state, the enhancer may physically associate with the promoter, triggering formation of a preinitiation complex and/or promoting the release of paused transcriptional complexes. Created with Biorender.com. RNA Pol II, RNA polymerase II; TF, transcription factor.