Induction of globin gene expression during erythroid cell differentiation.
We can provide increasing insight, albeit still incomplete, 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 (formula; see text) 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. The major increase in MELC globin gene transcription that is initiated by DMSO, HMBA, or butyric acid, is accompanied by, and perhaps preceded 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 transition during terminal differentiation in the erythroid cell lineage.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002843:Chromatin / Q000648:ultrastructure; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D003850:Deoxyribonuclease I; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D051379:Mice; D014158:Transcription, Genetic
D002843:Chromatin; D005914:Globins; D004248:DNA (Cytosine-5-)-Methyltransferases; D004706:Endodeoxyribonucleases; D003850:Deoxyribonuclease I