FIG. 7.

Two modes of LCR-promoter communication (tracking and looping) may control developmental stage- and/or gene-specific activation within the human β-globin locus. The 5′ and 3′ HSs (light blue ovals and numbered rectangles) may be involved in forming higher order chromatin architecture within the β-globin locus, one part of which is a powerful enhancer (the LCR). In primitive erythroid cells, the ɛ-globin gene may be activated by the LCR via tracking mechanism (WT, green arrow) and therefore displays sensitivity to the linear distance from the LCR (HS1/λ and ɛ/λ). Introduction of the CAC (presumptive EKLF binding) site into and/or disruption of the direct repeat sites from the ɛ-globin promoter (Bepsi) may allow it to be activated by means of a looping mechanism (arrow). Thus, the Bepsi promoter is highly active even after the λ DNA is inserted (HS1/λ/Bepsi). Predicted open chromatin domains are indicated.