Figure 4.

Simplified scheme of stepwise enhancer activation based on the pioneering model. A pioneer TF is exemplified by the ETS factor PU.1; the transcription start site (TSS) is indicated by a red or green arrow and the enhancer element is schematized by four nucleosomes. For simplicity, the nucleosomes covering the rest of the DNA including the promoter region are not indicated. (A) The pioneer TF recognizes and binds its cognate site in condensed chromatin. (B) Recruitment of histone methyltransferases (HMTs) and chromatin remodeling complexes (CRC) which prime the enhancer for subsequent activation. At this step, the enhancer now harbors H3K4me1 mark but still lacks acetylation marks. (C) Subsequent collaborative binding of downstream TFs accompanied by histone acetyl transferases (HATs) that catalyze histone acetylation, leading to enhancer activation and gene transcription.