Mapping of DNase I-hypersensitive sites in the upstream DNA of human embryonic ε-globin gene in K562 leukemia cells

D. Tuan, I. M. London

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Abstract

We have mapped the DNase I-hypersensitive sites around the ε-globin and c-myc genes in two human leukemia cells lines K562 and HL60. In K562 cells in which the ε-globin gene is transcribed, six DNase I-hypersensitive sites are found in 6 kilobases (kb) of upstream flanking DNA; in HL60 cells in which the c-myc gene is expressed, two DNase I-hypersensitive sites are observed in 2 kb of upstream DNA. Neither the inactive ε-globin gene in HL60 cells nor the inactive c-myc gene in K562 cells displays such upstream DNase I-hypersensitive sites. Our results are consistent with previous studies that have shown DNase I-hypersensitive sites within 1 kb of the 5' end of other expressed genes. In addition, we have found sites displaying even more DNase I sensitivity further upstream of expressed ε-globin and c-myc genes. Among the six DNase I-hypersensitive sites of the expressed ε-globin gene in K562 cells, the most sensitive site is located about 6 kb upstream of the ε-globin gene. When correlated with the DNA sequence upstream of the ε-globin gene, this site was found to correspond to a region that contains a stretch of 28 consecutive Ts, three enhancer core-like sequences, and a stretch of consecutive (C-A)15(T-A)6 alternating purine and pyrimidine bases. These findings suggest the possibility that an enhancer element for ε-globin gene expression resides within this DNase I-hypersensitive site.

Original languageEnglish (US)
Pages (from-to)2718-2722
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume81
Issue number9 I
DOIs
StatePublished - Jan 1 1984

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