title: Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region.
abstract: Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to the genes of the beta-globin cluster. A tandem repeat of the consensus sequence for the transcription factors AP1 and NF-E2 (activating protein 1 and nuclear factor erythroid 2, respectively) is present within hypersensitive site 2 and is absolutely required for strong enhancer activity. This sequence binds, in vitro and in vivo, to ubiquitous proteins of the AP1 family and to the recently cloned erythroid-specific transcription factor NF-E2. Using the tandem repeat as a recognition site probe to screen a lambda gt11 cDNA expression library from K562 cells, we isolated several DNA binding proteins. Here, we report the characterization of one of the clones isolated. The gene, which we named Nrf2 (NF-E2-related factor 2), is encoded within a 2.2-kb transcript and predicts a 66-kDa protein with a basic leucine zipper DNA binding domain highly homologous to that of NF-E2. Although Nrf2 is expressed ubiquitously, a role of this protein in mediating enhancer activity of hypersensitive site 2 in erythroid cells cannot be excluded. In this respect, Nrf2 contains a powerful acidic activation domain that may participate in the transcriptional stimulation of beta-globin genes.
authors.affiliation: Istituto di Clinica e Biologia dell' Età Evolutiva, Università di Cagliari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Moi
authors.forename: K
authors.initials: K
authors.lastname: Chan
authors.forename: I
authors.initials: I
authors.lastname: Asunis
authors.forename: A
authors.initials: A
authors.lastname: Cao
authors.forename: Y W
authors.initials: YW
authors.lastname: Kan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002460:Cell Line; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D015870:Gene Expression; D015723:Gene Library; D005809:Genes, Regulator; D005914:Globins / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D005810:Multigene Family; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; D009838:Oligodeoxyribonucleotides; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; C494692:NFE2 protein, human; C495635:NFE2L2 protein, human; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D005914:Globins