Cited by 1,607Hemoglobinopathies and Related DisordersGenomics and Chromatin DynamicsGenomics, phytochemicals, and oxidative stress

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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

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Moi, P, Chan, K, Asunis, I, Cao, A, Kan, Y W·1994·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.91.21.9926PMC PMC44930

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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.

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Authors: Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W.
Affiliations: University of Cagliari (IT)
Howard Hughes Medical Institute (US)
ORCID: Moi, P
Asunis, I
Kan, Y W
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1994-10-11
Volume: 91
Issue: 21
Pages: 9926-9930
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.91.21.9926
PMC: PMC44930
OpenAlex: W1991265255
Cited by: 1,607
References: 41
Citations by year: 2026: 38 · 2025: 71 · 2024: 102 · 2023: 96 · 2022: 111 · 2021: 89 · 2020: 89 · 2019: 87 · 2018: 61 · 2017: 65 · 2016: 59 · 2015: 68 · 2014: 77 · 2013: 65 · 2012: 72
FWCI: 10.89
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
University of California, San Francisco
National Institute of Diabetes and Digestive and Kidney Diseases (DK16666)
Topics: Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: Nrf2, NF-E2, beta-globin locus control region, AP-1, bZIP transcription factors, erythroid-specific transcription factors, acidic activation domain, transcriptional activation, beta-globin gene expression, K562 cells
MeSH terms: Amino Acid Sequence, Base Sequence, Binding Sites, Cell Line, DNA-Binding Proteins, Leukemia, Erythroblastic, Acute, Genes, Regulator, Multigene Family, Globins, Humans, Molecular Sequence Data, Oligodeoxyribonucleotides, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Transcription Factors, Tumor Cells, Cultured, Blotting, Northern, Trans-Activators, Gene Library, Gene Expression, Zinc Fingers, Leucine Zippers, Open Reading Frames, Consensus Sequence, Sequence Homology, Amino Acid, Transcription Factor AP-1, Erythroid-Specific DNA-Binding Factors, NF-E2 Transcription Factor, NF-E2 Transcription Factor, p45 Subunit, NF-E2-Related Factor 2

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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

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