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

Non-coding exons of epsilon-globin mRNA originating within the 236 kb upstream region of the epsilon-globin gene were identified in human primary tissues and K562 cells. One predominant type of upstream epsilon mRNA, which originated in the -76 kb region 5' to the epsilon 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 approximately 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 beta-globin gene cluster.