Heavy metals have been shown to inhibit the binding of Sp1. This study shows that "knock down of Egr-1 or Sp1 prevents promoter activation while siRNA knock down of HIF1α inhibits Egr-1 and Sp1 induction. Findings suggest that hypoxia activates the PNMT gene indirectly via HIF1α stimulation of Egr-1 and Sp1. Thus, for stress-induced illnesses where adrenergic dysfunction is implicated, HIF1α may be an "on-off" switch regulating adrenergic responses to stress and a potential target for therapeutic intervention."
Wong, D. L. L.
et al. Stress and Adrenergic Function: HIF1α, a Potential Regulatory Switch.
Cellular and molecular neurobiology 1-7 (2010). URL
http://dx.doi.org/10.1007/s10571-010-9567-z.