Figure 7. Super-enhancers acting as chromatin sensors of the extracellular milieu control the identity and memory of renin cells to maintain homeostasis.

See main text for details. The inset illustrates events that occur in renin cells in order to maintain or reenact the renin phenotype. The cAMP pathway is activated through the β-adrenergic receptor or the prostaglandin E2 receptor. Phosphorylated CREB enters the nucleus and binds the CRE element at the enhancer of the renin gene. As the Notch receptor is activated by cell-cell interaction, its intracellular domain (NICD) enters the nucleus and binds the transcription factor RBPJ. As these events occur, the chromatin is made accessible at the renin locus, which is characterized by the deposition of H3K27ac due to p300 histone acetyl transferase activity; MED1 establishes the bridge between the renin enhancer and Pol II. These key components act together to activate the transcriptional machinery. Moreover, other super-enhancers (color dots) may cooperate to fully establish the renin phenotype. β-AR, beta adrenergic receptor; PGE_2, prostaglandin E_2; AC, adenylate cyclase; Gs_α, activating G protein–coupled subunit; PKA, protein kinase A; CREB^P, phosphorylated cAMP responsive element binding protein.