Non-coding transcripts far upstream of the ε-globin gene are distinctly expressed in human primary tissues and erythroleukemia cell lines

Non-coding exons of ε-globin mRNA originating within the 236 kb upstream region of the ε-globin gene were identified in human primary tissues and K562 cells. One predominant type of upstream ε mRNA, which originated in the −76 kb region 5′ to the ε gene, was present in human primary tissues, whereas 11 other isoforms were identified in K562 cells. Fragment from the −76 kb region possessed promoter activity and a prominent DNase I hypersensitive site was formed in the region ∼2 kb 5′ to the −76 kb promoter in human fetal liver, but not in K562 cells. The promoter activity in the −236 kb region resided in a retrotransposon in K562 cells. A DNase I hypersensitive site was formed at the −236 kb promoter in K562 cells, but not in human fetal liver. We discussed these results in the context of intergenic transcription and chromatin opening in the β-globin gene cluster.