We have addressed the possible role of DNA:RNA triple helix formation in regulation of gene expression, particularly in the human beta globin gene locus. There are strict rules for the combinations of bases that can form such structures. We searched for loci that obeyed those rules. Most significantly we have found that an intronic sequence within the adult human beta globin primary transcript can form a triple helix with a target site in the beta globin locus control region (LCR), the major positive compound regulatory element of the beta globin genes. We show that when a full length transcript containing the wild type second beta globin intron is overexpressed it downregulates expression of globin genes by binding to a site in the LCR and displacing transcription factors. A transcript that is identical but with the intronic triplex forming sequence mutated has no effect. This appears to be a feedback system to prevent overexpression of the beta globin genes. We have found another example of this regulation elsewhere in the genome, suggesting that this may a general regulatory mechanism.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Planutis, Antanas; Xue, Li; Trainor, Cecelia D et al. (2017) Neomorphic effects of the neonatal anemia (Nan-Eklf) mutation contribute to deficits throughout development. Development 144:430-440
Hasegawa, Atsushi; Kaneko, Hiroshi; Ishihara, Daishi et al. (2016) GATA1 Binding Kinetics on Conformation-Specific Binding Sites Elicit Differential Transcriptional Regulation. Mol Cell Biol 36:2151-67
Zhu, Jianqiong; Chin, Kyung; Aerbajinai, Wulin et al. (2011) Recombinant erythroid Kruppel-like factor fused to GATA1 up-regulates delta- and gamma-globin expression in erythroid cells. Blood 117:3045-52
Giles, K E; Gowher, H; Ghirlando, R et al. (2010) Chromatin boundaries, insulators, and long-range interactions in the nucleus. Cold Spring Harb Symp Quant Biol 75:79-85
Trainor, Cecelia D; Mas, Caroline; Archambault, Patrick et al. (2009) GATA-1 associates with and inhibits p53. Blood 114:165-73