FIG 2.

Embryonic and fetal globin gene repression by the DRED complex and molecular targets of inhibitory drugs. The DRED complex directly binds to the promoters of the embryonic and fetal globin genes to repress their expression in definitive adult bone marrow-derived erythroid progenitor cells. The DRED core tetrameric complex is composed of TR2/TR4, DNMT1, and LSD1. The core complex also associates with additional corepressors (NuRD and CoREST complexes that contain HDACs 1 and 2 and independently with HDAC3). Inhibitors of DNMT, LSD1, and HDACs, namely, 5-azacytidine/decitabine, tranylcypromine, and butyrate, respectively, induce fetal globin expression, which is at least partially dependent on DRED activity.