title: CP2 binding to the promoter is essential for the enhanced transcription of globin genes in erythroid cells.
abstract: We have previously reported that the reduced level of CP2 suppresses the mouse alpha- and beta-globin gene expression and hemoglobin synthesis during terminal differentiation of mouse erythroleukemia (MEL) cells in vitro [Chae et al. (1999)]. As an extension of this study, we demonstrated that human alpha-, epsilon-, and gamma- globin genes were also suppressed by the reduced expression of CP2 in K562 cells. To address how much CP2 contributes in the regulation of globin gene expression, we measured transcriptional activities of the wild type alpha-globin promoter and its various factor-binding sites mutants in erythroid and nonerythroid cells. Interestingly, CP2 site dependent transcriptional activation occurred in an erythroid-cell specific manner, even though CP2 is ubiquitously expressed. In addition, CP2 site mutation within the alpha-promoter severely suppressed promoter activity in differentiated, but not in undifferentiated MEL cells, suggesting that the CP2 binding site is needed for the enhanced transcription of globin genes during erythroid differentiation. When the human beta-globin locus control region was linked to the alpha-promoter, suppression was more severe in the CP2 site mutant in differentiated MEL cells. Overall data indicate that CP2 is a major factor in the regulation of globin expression in human and mouse erythroid cells, and CP2 binding to the globin gene promoter is essential for the enhanced transcription of globin genes in erythroid differentiation.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chae
authors.forename: Chul Geun
authors.initials: CG
authors.lastname: Kim
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D005813:Genes, Synthetic; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020014:K562 Cells / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D005914:Globins