The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.
Open accessAbstract
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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In the citing paper
“which coordinate transcriptional and post-transcriptional programs that promote metabolic adaptation, angiogenesis, erythropoiesis, and redox balance”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [30]
In the citing paper
“hypoxia-inducible factors (HIFs) form the central transcriptional axis governing cellular adaptation to oxygen deprivation”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [30]
In the citing paper
“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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Cited by
Sorted by citations
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981
Self-citationSemenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Self-citationPurification and Characterization of Hypoxia-inducible Factor 1
Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094
Self-citationRegulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914
Self-citationTranscriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Self-citation
Metadata
- Authors
- Semenza, G. L., Nejfelt, M. K., Chi, S. M., & Antonarakis, S. E.
- Affiliations
- Johns Hopkins University (US)
- 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
- 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 › Biochemistry › 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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