We can provide increasing insight, albeit still incomplete, into the changes in MELC that accompany induced globin gene expression. It is suggested that these transformed CFU-E-like erythroid precursor cells exhibit in their uninduced state a DNA methylation pattern and globin gene chromatin configuration (DNase I sensitivity) that is compatible with actual or potential gene transcription. Such features may reflect alterations in chromatin configuration that occurred earlier, during the differentiation of erythroid precursor cells, which is associated with the restriction in developmental potential that is characteristic of progression to the CFU-E (or MELC) stage of erythropoiesis. Uninduced MELC display a low level of globin gene transcription, producing globin mRNA or mRNA precursors whose processing or stabilization is the site of action of hemin. The major increase in MELC globin gene transcription that is initiated by HMBA or butyric acid is accompanied by an increase in DNase I hypersensitivity in the regions 5' to the active globin genes. This suggests that reorganization of chromatin structure in the globin gene domains is associated with accelerated globin gene transcription and may be characteristic of a developmental stage transition during terminal differentiation in the erythroid cell lineage.