Evidence for a globin promoter-specific silencer element located upstream of the human delta-globin gene

Biochemical and Biophysical Research Communications
M VitaleA Maggio

Abstract

We describe the negative regulatory activity of a 1.7 kilobase (kb) region (R) in the human beta-globin locus located between 4.0 and 2.3 kb upstream of the delta-globin gene capsite, using a transient assay with the chloramphenicol acetyltransferase (CAT) reporter gene in mouse erythroleukemia (MEL) cells. The R region is deleted in most cases of deletion hereditary persistence of fetal hemoglobin (HPFH), but is unaffected in most delta beta zero-thalassemias. However, no experiments addressing its function in globin gene expression have been reported to date. We show that R inhibits CAT expression of constructs containing a fetal (gamma) or adult (beta) globin gene promoter, but does not affect expression of similar constructs using a non-globin (SV40) promoter. The inhibitory effect on the beta-globin promoter can be localized to a 651 bp sub-region of R. For the gamma-globin promoter, no sub-region of R can reproduce the level of inhibition associated with the entire region.

Citations

Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Karin M L GaenslerLinda Flebbe-Rehwaldt
Oct 13, 2006·American Journal of Hematology·Saovaros SvastiSuthat Fucharoen
Mar 29, 2002·Pediatric Research·Antonio Cao, Paolo Moi
Feb 26, 1999·The Journal of Biological Chemistry·J M Grégoire, P H Roméo

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