A model of dynamic long-range communication between the β-globin LCR and gene. Association of the Ldb1 complex (GATA-1/SCL/LMO2) and other activation components (shaded ovals), whose recruitment might be dependent on Ldb1, occupying the LCR and β-globin gene. Previous work comparing induced and uninduced MEL cells suggests that the Ldb1 complex binds first to the LCR.¹¹  In the absence of the LCR, these components can co-occupy the β-globin gene, implying that promoter occupancy may normally occur independently; however, such occupancy is insufficient for high-level transcription. Full occupancy may be sufficient to establish LCR/β-globin proximity, before nuclear migration, via unknown mechanisms, and TF occupancy. Alternatively, the locus might migrate, again by unknown mechanisms, and establish LCR/β-globin proximity as a result of positioning within a TF. Proximity would then be stabilized by protein-protein interactions, possibly dependent on Ldb1.