A casual examination of the globin literature would leave most readers with the impression that all aspects of beta-globin gene regulation are controlled by the upstream locus control region (LCR). There is no clear evidence, however, that the LCR affects transcription in the beta-globin locus other than by altering its topology to maintain it in a state permissive for expression of the globin genes. Developmental switching of the globin genes may be independent of the LCR, relying only on elements close to the genes and the arrangement of the genes with respect to each other.