Induction of Globin Gene Expression during Erythroid Cell Differentiation

Murine erythroleukemia cells (MELC) are transformed erythroid cell precursors that may be induced, by a variety of agents, including DMSO, to initiate the program of terminal cell differentiation and cell division characteristic of normal ertyropoiesis. We can provide increasing insight into the changes in MELC that accompany globin gene expression induced by polar chemicals, such as DMSO, and other agents. These transformed, CFUe-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 have occurred at a stage prior to leukemic transformation, during the differentiation of earlier erythroid precursor cells and associated with the restriction in developmental potential characteristic of progression to the CFUe (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 target of action of hemin.
This article is from 'Conference on Biological Actions and Medical Applications of Dimethyl Sulfoxide (DMSO), 15-17 September 1982,' AD-A133 175. p141-149.