A. Heme facilitates GATA1 activity via BACH1. GATA1 activates Bach1 transcription. In heme-deficient cells, BACH1 protein accumulates, binds BACH1 DNA motifs, and opposes GATA1 activity to activate target gene transcription. In a normal heme environment, BACH1 protein proteolysis dominates over mechanisms that promote BACH1 synthesis, thus negating the mechanism that antagonizes GATA1.
B. Heme facilitates GATA1 activity via HERM. The presence of a HERM-binding transcriptional activator or the absence of a HERM-binding repressor in a physiological heme environment facilitates GATA1-mediated activation of target gene transcription.