Figure 2.

Elastin (ELN, 2.2 kb) gene promoter structure. The human ELN gene lacks a conventional TATA box but contains at least two CAAT boxes and multiple transcription start sites. Several cytokines are known to affect ELN promoter activity. Cytokines that are generally ELN transcription are in green whereas cytokines that generally lead to decreased ELN transcription are in magenta. Arrows represent interactions that promote transcription factor binding to the promoter whereas inhibitory interactions are denoted by arrows with flat heads. Transcription factors that promote ELN transcription are purple, those that inhibit transcription are orange. There are multiple GC boxes that enable Sp1 binding clustered close to the initiation methionine. SP1 interacts with activated Rb to promote transcription in response to TGFb1 and insulin like growth factor-1 (IGF1). Sp1 binding to the promoter is disrupted by IL1b and PDGF. IL1b also promotes binding of C/EBPb to the proximal CAAT box, inhibiting transcription. There are also multiple AP1 binding sites. A proximal AP1 binding site inhibits ELN transcription through the binding of JUN homodimers in response to TNFa while a more distal AP1 site inhibits ELN expression in response to multiple cytokines. There are three glucocorticoid response elements (GRE) that promote transcription in the presence of glucocorticoids such as dexamethasone or hydrocortisone although this appears to be cell type and state specific. Evidence also suggests that insulin can promote ELN transcription through release of inhibitory FoxO1 binding. Created with BioRender.com.