Figure 7. Model for HIF-1 iron-dependent activation and inhibition of intestinal iron uptake and storage.Iron sufficiency: ELT-2 binds to GATA binding sites located in the
ftn-1 and
ftn-2 IDEs. We propose that ELT- 2 cooperates with an unidentified transcriptional activator (ACT) that binds to the HREs and enhances transcription.
smf-3 is transcribed at basal levels during iron sufficiency. HIF-1 is expressed during normal growth conditions, but at low levels. Iron deficiency: HIF-1 is stabilized and dimerizes with AHA-1. HIF-1/AHA-1 (denoted by HIF-1) displaces the unidentified transcriptional activator binding to the
ftn-1 and
ftn-2 HREs and inhibits transcription. HIF-1/AHA-1 binds to the
smf-3 HREs, recruits coactivators and cooperates with ELT-2 to enhance
smf-3 transcription. Whether ELT-2 is bound to the
ftn-1 GATA sites during iron deficiency and to the
smf-3 GATA sites during iron sufficiency has not been determined.