Multiple regulatory elements in the 5'-flanking sequence of the human epsilon-globin gene.

The Journal of Biological Chemistry
J LiA N Schechter

Abstract

We have previously reported, on the basis of transfection experiments, the existence of a silencer element in the 5'-flanking region of the human embryonic (epsilon) globin gene, located at -270 base pairs 5' to the cap site, which provides negative regulation for this gene. Experiments in transgenic mice suggest the physiological importance of this epsilon-globin silencer, but also suggest that down-regulation of epsilon-globin gene expression may involve other negative elements flanking the epsilon-globin gene. We have now extended the analysis of epsilon-globin gene regulation to include the flanking region spanning up to 6 kilobase pairs 5' to the locus control region using reporter gene constructs with deletion mutations and transient transfection assays. We have identified and characterized other strong negative regulatory regions, as well as several positive regions that affect transcription activation. The negative regulatory regions at -3 kilobase pairs (epsilonNRA-I and epsilonNRA-II), flanked by a positive control element, has a strong effect on the epsilon-globin promoter both in erythroid K562 and nonerythroid HeLa cells and contains several binding sites for transcription factor GATA-1, as evidenced from DNA-prote...Continue Reading

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Citations

Jul 4, 2002·Molecular Aspects of Medicine·Thomas Brittain
Jan 23, 1999·American Journal of Human Genetics·J C Schimenti
Jul 13, 2005·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Elisa PieragostiniAldo Di Luccia
Dec 27, 2005·Molecular and Cellular Endocrinology·Ekaterina BreousUlrich Loos
Apr 14, 2007·The EMBO Journal·Osamu TanabeJames Douglas Engel
Sep 27, 2002·Experimental Biology and Medicine·Susanna HarjuKenneth R Peterson
Mar 4, 2006·Experimental Biology and Medicine·Patrick A NavasGeorge Stamatoyannopoulos

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