Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

Semenza, G L; Nejfelt, M K; Chi, S M; Antonarakis, S E

doi:10.1073/pnas.88.13.5680

Cited by 992Erythropoietin and Anemia TreatmentCancer, Hypoxia, and MetabolismHemoglobin structure and function

Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

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Semenza, G L, Nejfelt, M K, Chi, S M, Antonarakis, S E·1991·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.88.13.5680PMC PMC51941

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Abstract

Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia.

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“which coordinate transcriptional and post-transcriptional programs that promote metabolic adaptation, angiogenesis, erythropoiesis, and redox balance”
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“hypoxia-inducible factors (HIFs) form the central transcriptional axis governing cellular adaptation to oxygen deprivation”
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Deoxygenation can activate the hypoxia-inducible factor (HIF) transcription system, which triggers the expression of most genes responsible for cellular adaptation to varying O2 levels.
“deoxygenation can also activate the hypoxia-inducible factor (HIF) transcription system, which triggers the expression of most genes responsible for cellular adaptation to varying O2 levels (Semenza et al., 1991; Wang et al., 1995; Semenza, 2012).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Semenza et al., 1991

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Authors: Semenza, G. L., Nejfelt, M. K., Chi, S. M., & Antonarakis, S. E.
Affiliations: Johns Hopkins University (US)
ORCID: Semenza, G L
Antonarakis, S E
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1991-07
Volume: 88
Issue: 13
Pages: 5680-5684
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.88.13.5680
PMC: PMC51941
OpenAlex: W2090627731
Cited by: 990
References: 25
Citations by year: 2026: 24 · 2025: 35 · 2024: 46 · 2023: 58 · 2022: 43 · 2021: 53 · 2020: 62 · 2019: 34 · 2018: 26 · 2017: 30 · 2016: 38 · 2015: 30 · 2014: 22 · 2013: 41 · 2012: 25
FWCI: 8.88
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords: erythropoietin gene, hypoxia-inducible factor, enhancers, 3' flanking region, DNase I hypersensitive sites, anemia, hypoxia, gene expression regulation, liver, kidney, transcription factor binding
MeSH terms: Animals, Hypoxia, Base Sequence, Cell Nucleus, Chromosome Mapping, Deoxyribonuclease I, DNA-Binding Proteins, Enhancer Elements, Genetic, Erythropoietin, Gene Expression Regulation, Genes, Humans, Mice, Transgenic, Molecular Sequence Data, Nuclear Proteins, Regulatory Sequences, Nucleic Acid, Restriction Mapping, Mice

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Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

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