Besides, HDAC1 reduces expression of hepcidin by interacting with SMAD4 rather than deacetylation of SMAD4 or histone-H3 on the hepcidin promoter (112); therefore, it is interesting to further investigate whether iron deficiency directs pro-inflammatory macrophage polarization that is independent of the effect of deacetylation of HDAC1. The gene discussed is SMAD4; the disease is Iron deficiency anemia.