FIGURE 2.

Model for HIF-1 iron-dependent activation and inhibition of intestinal iron uptake and storage in C. elegans. 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 hypoxia-response elements (HREs) to regulate transcription. As HREs resemble E-box elements, which are binding sites for bHLH transcription factors, it is possible that a bHLH transcription factor serves this role. smf-3 is transcribed at basal levels during iron sufficiency to limit iron absorption. HIF-1 is expressed during normal growth conditions, but at low levels. Iron deficiency: HIF-1 accumulates and dimerizes with AHA-1. HIF-1/AHA-1 (denoted by HIF-1) displaces the transcriptional activator ACT binding to the ftn-1 and ftn-2 HREs and inhibits transcription. Another possible mechanism for HIF-1 mediated ftn-1 repression is the displacement of ELT-2 by HIF-1. HIF-1/AHA-1 binds to the smf-3 HREs, recruits coactivators (CoA) and cooperates with ELT-2 to activate 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. (Adapted from Romney et al., 2011).