DNA·RNA triple helix formation can function as a cis -acting regulatory mechanism at the human β-globin locus

Significance RNA containing only pyrimidines, transcribed from genomic DNA, can form DNA∙RNA triple helices with other sites in the genome. We characterize an intronic sequence in the human β-globin gene that forms a triplex with an upstream regulatory site in the β-globin locus, causing displacement of transcription factors and down regulation of expression of the genes in the locus. Consequently, overexpression of a full-length β-globin transcript containing the intron results in decreased expression of members of the β-globin gene cluster. This is a cis -regulatory feedback mechanism in which overexpression of the β-globin gene could result in signals to down-regulate that expression. Balance in the expression of the many genes associated with hemoglobin biosynthesis is essential for erythroid cell function.