Alterations in globin gene chromatin conformation during murine erythroleukemia cell differentiation

Adult beta-globin gene chromatin in murine erythroleukemia (MEL) cells acquired increased sensitivity to both micrococcal nuclease and DNase I during hexamethylenebisacetamide-induced erythoid differentiation. The DNase I hypersensitivity of the globin genes accompanied their actual transcription and was strongly correlated with commitment events. On the other hand, the rate of micrococcal nuclease digestion was closely related to the rate of globin gene transcription. Two distinct DNase I hypersensitive sites were found on the 5' side of the beta-major globin gene in HMBA-induced cells. One site was located near the 5' side of the beta-major globin gene and the second site was located approximately 3 kilobases upstream of the beta-major cap site. Following the commitment of MEL cells to differentiate, DNase I sensitivity was stably inherited in the absence of inducer. In contrast to HMBA, another inducer, hemin, known to cause the accumulation of globin-specific mRNA in MEL cells by a post-transcriptional mechanism, did not elicit alterations of beta-globin gene chromatin. The addition of dexamethasone, a hormone known to inhibit MEL cell commitment, blocked the formation of general and site-specific nuclease sensitivity of beta-globin gene chromatin prior to but not after cell commitment.