BP1 motif in the human beta-globin promoter affects beta-globin expression during embryonic/fetal erythropoiesis in transgenic mice bearing the human beta-globin gene.
The binding of the transcription factor BP1 (beta protein 1) to its site on the promoter of the adult beta-globin gene has a silencing effect on beta-globin transcription in vitro. To better understand the mechanism of BP1's negative regulation of beta-globin expression, we developed transgenic mice bearing a human beta-globin locus-containing cosmid. Specifically, we introduced a mutated BP1 binding site (mtBP1) into the promoter of the beta-globin gene sequence of this cosmid construct. In the mtBP1 mice, we detected a more than a 20-fold increase in human beta-globin expression in the yolk sac-derived blood at E10.5, a 3-fold increase in fetal livers at E13.5, and an approximately 1.4-fold increase in adult reticulocytes compared with control mice bearing the human beta-globin gene with the wild-type BP1 binding site sequence (wtBP1). Our in vivo observations support the contention that the BP1 binding site of the beta-globin promoter plays an important role in the regulation of transcription of the adult beta-globin gene.
Zoueva
Olga P
OP
Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH 9000 Rockville Pike, Building 31, Room 9A52, Bethesda, MD 20892, USA.
Garrett
Lisa J
LJ
Bodine
David
D
Rodgers
Griffin P
GP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003360:Cosmids / Q000235:genetics; D004920:Erythropoiesis; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
C105304:DLX4 protein, human; C104149:Dlx4 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D055544:beta-Globins