Erythroid-specific nuclease-hypersensitive sites flanking the human beta-globin domain.
Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.
Dhar
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Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Nandi
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Schildkraut
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Skoultchi
A I
AI
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism*; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D009710:Nucleotide Mapping; D015183:Restriction Mapping; D013379:Substrate Specificity; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004273:DNA, Neoplasm; D005914:Globins; D003850:Deoxyribonuclease I