Cited by 990Erythropoietin and Anemia TreatmentCancer, Hypoxia, and MetabolismHemoglobin structure and function

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 access

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.88.13.5680

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
History of Erythropoiesis-Stimulating Agents, the Development of Biosimilars, and the Future of Anemia Treatment in Nephrology
Kalantar‐Zadeh, K. (2017) · American Journal of Nephrology · doi:10.1159/000455387 · Cited by 1,149
Cloning and expression of the human erythropoietin gene.
Lin, F. K., Suggs, S. V., Lin, C.-W., Browne, J. K., Smalling, R., Egrie, J. C., Chen, K. K., Fox, G. M., Martin, F., & Stabinsky, Z. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.22.7580 · Cited by 1,131
Regulation of the Erythropoietin Gene: Evidence That the Oxygen Sensor Is a Heme Protein
Goldberg, M. A., Dunning, S. P., & Bunn, H. F. (1988) · Science · doi:10.1126/science.2849206 · Cited by 1,032
Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses.Preprint
Jones, N., Rigby, P. W. J., & Ziff, E. B. (1988) · Genes & Development · doi:10.1101/gad.2.3.267 · Cited by 675
Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene
Graves, B. J., Johnson, P. F., & McKnight, S. L. (1986) · Cell · doi:10.1016/0092-8674(86)90266-7 · Cited by 533
Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization
Koury, S., Bondurant, M. C., & Koury, M. (1988) · Blood · doi:10.1182/blood.v71.2.524.524 · Cited by 469
Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells.
Kourembanas, S., Hannan, R. L., & Faller, D. V. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114759 · Cited by 386
The regulated expression of erythropoietin by two human hepatoma cell lines.
Goldberg, M. A., Glass, G. A., Cunningham, J. M., & Bunn, H. F. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.22.7972 · Cited by 358
Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization: correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration
Koury, S. T., Koury, M., Bondurant, M. C., Caro, J., & Gräber, S. E. (1989) · Blood · doi:10.1182/blood.v74.2.645.645 · Cited by 252

Show all 25 references

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-citation
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Self-citation
Purification 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-citation
Regulation 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-citation
Transcriptional 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
Metabolic reprogramming in macrophages and dendritic cells in innate immunity
Kelly, B., & O'Neill, L. A. (2015) · Cell Research · doi:10.1038/cr.2015.68 · Cited by 1,876
HIF-1α pathway: role, regulation and intervention for cancer therapy
Masoud, G. N., & Li, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.05.007 · Cited by 1,871
“LW6 (15) decreases HIF-1α protein expression through potentiating VHL expression, which in turn interacts with prolylhydroxylated HIF-1α for proteasomal degradation.”
Background
Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions
Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674
Hypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,690
HIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4304 · Cited by 1,468
Self-citation
The impact of O2 availability on human cancer
Bertout, J. A., Patel, S. A., & Simon, M. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2540 · Cited by 1,365
Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension
Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.4.c1172 · Cited by 1,213
Self-citation
Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit
Huang, E. L., Arany, Z. P., Livingston, D. M., & Bunn, H. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32253 · Cited by 1,204
Cellular adaptation to hypoxia: O 2 ‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O 2 ‐regulated gene expression
Wenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135
Hypoxia-inducible factor 1: master regulator of O2 homeostasis
Semenza, G. L. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80016-6 · Cited by 1,092
Self-citation
The PAS Superfamily: Sensors of Environmental and Developmental Signals
Gu, Y.-Z., Hogenesch, J. B., & Bradfield, C. A. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.519 · Cited by 1,044
AH RECEPTOR SIGNALING PATHWAYS
Schmidt, J. V., & Bradfield, C. A. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.55 · Cited by 899
Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia
Guzy, R. D., & Schumacker, P. T. (2006) · Experimental Physiology · doi:10.1113/expphysiol.2006.033506 · Cited by 881
Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80571-7 · Cited by 863
Self-citation
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
Diversity of degradation signals in the ubiquitin–proteasome system
Ravid, T., & Hochstrasser, M. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2468 · Cited by 859
Differential Transcriptional Regulation of the Two Vascular Endothelial Growth Factor Receptor Genes
Gerber, H.-P., Condorelli, F., Park, J., & Ferrara, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23659 · Cited by 794
The role of HIF in immunity and inflammation
McGettrick, A. F., & O’Neill, L. A. J. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.08.002 · Cited by 768
Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction
Wang, G., & Semenza, G. (1993) · Blood · doi:10.1182/blood.v82.12.3610.3610 · Cited by 766
Self-citation
High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq
Schödel, J., Oikonomopoulos, S., Ragoussis, J., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2011) · Blood · doi:10.1182/blood-2010-10-314427 · Cited by 724
Erythropoietin: Physiology and Pharmacology Update
Fisher, J. W. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322800101 · Cited by 707
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Kaur, B., Khwaja, F. W., Severson, E. A., Matheny, S. L., Brat, D. J., & Van Meir, E. G. (2005) · Neuro-Oncology · doi:10.1215/s1152851704001115 · Cited by 725
Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1α-degradative pathway
Isaacs, J. S., Jung, Y.-J., Mimnaugh, E. G., Martinez, A., Cuttitta, F., & Neckers, L. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204733200 · Cited by 663
Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641
Self-citation
Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α
Jiang, B.-H., Zheng, J. Z., Leung, S. W., Roe, R., & Semenza, G. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19253 · Cited by 629
Self-citation
Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis: applications and therapies
Zimna, A., & Kurpisz, M. (2015) · BioMed Research International · doi:10.1155/2015/549412 · Cited by 604
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596
Zonation of parenchymal and nonparenchymal metabolism in liver.
Jungermann, K., & Keitzmann, T. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001143 · Cited by 589
Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.
Gu, Y.-Z., Moran, S. M., Hogenesch, J. B., Wartman, L. D., & Bradfield, C. A. (1998) · Europe PMC (PubMed Central) · Cited by 577
HIF1 and oxygen sensing in the brain
Sharp, F. R., & Bernaudin, M. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1408 · Cited by 579
Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00003-3 · Cited by 559
Cellular Mechanism of Oxygen Sensing
López‐Barneo, J., Pardal, R., & Ortega‐Sáenz, P. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.259 · Cited by 551
Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer.
Firth, J. D., Ebert, B. L., Pugh, C. W., & Ratcliffe, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6496 · Cited by 525
Pathological angiogenesis: mechanisms and therapeutic strategies
Dudley, A. C., & Griffioen, A. W. (2023) · Angiogenesis · doi:10.1007/s10456-023-09876-7 · Cited by 571
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499
Targeting Proteins for Destruction by the Ubiquitin System: Implications for Human Pathobiology
Schwartz, A. L., & Ciechanover, A. J. (2008) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.051208.165340 · Cited by 498
Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival
Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter, K. C., & Harris, A. L. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2018 · Cited by 478
Hypoxic gene expression and metastasis
Le, Q., Denko, N. C., & Giaccia, A. J. (2004) · Cancer and Metastasis Reviews · doi:10.1023/b:canc.0000031768.89246.d7 · Cited by 467
Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments
Wei, X., Chen, Y., Jiang, X., Miao, P., Liu, Y., Mo, Y., Ren, D., Hua, Y., Yu, B., Zhou, Y., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-020-01288-1 · Cited by 477
A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes.
Masuda, S., Okano, M., Yamagishi, K., Nagao, M., Ueda, M., & Sasaki, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32195-6 · Cited by 464
Mitochondrial complex III regulates hypoxic activation of HIF
Klimova, T., & Chandel, N. S. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402307 · Cited by 433
Inducible operation of the erythropoietin 3' enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism.
Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2423 · Cited by 411
Multi-functional nanocarriers to overcome tumor drug resistance
Milane, L. S., van Vlerken, L. E., Yadav, S. K., & Amiji, M. M. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2008.04.003 · Cited by 409
Hypoxia-induced reactive oxygen species formation in skeletal muscle
Clanton, T. L. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01298.2006 · Cited by 401
Placental but Not Heart Defects Are Associated with Elevated Hypoxia-Inducible Factor α Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2
Takeda, K., Ho, V. C., Takeda, H., Duan, L.-J., Nagy, A., & Fong, G.-H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00425-06 · Cited by 401
Differentiating the functional role of hypoxia‐inducible factor (HIF)‐1α and HIF‐2α (EPAS‐1) by the use of RNA interference: erythropoietin is a HIF‐2α target gene in Hep3B and Kelly cells
Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V. A., Frei, U. A., Wiesener, M. S., & Eckardt, K. (2004) · The FASEB Journal · doi:10.1096/fj.04-1640fje · Cited by 406
Identification of the renal erythropoietin-producing cells using transgenic mice
Maxwell, P. H., Osmond, M. K., Pugh, C. W., Heryet, A. R., Nicholls, L. G., Tan, C. C., Doe, B., Ferguson, D. J. P., Johnson, M. H., & Ratcliffe, P. J. (1993) · Kidney International · doi:10.1038/ki.1993.362 · Cited by 388
Oxygen, a source of life and stress
Brahimi-Horn, M. C., & Pouysségur, J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.06.018 · Cited by 383
ENDOTHELIAL CELL RESPONSES TO HYPOXIC STRESS
Faller, D. V. (1999) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.1999.02992.x · Cited by 372
Oxygen Sensing, Hypoxia-Inducible Factor-1 and the Regulation of Mammalian Gene Expression
Ratcliffe, P. J., O’rourke, J. F., Maxwell, P. H., & Pugh, C. W. (1998) · Journal of Experimental Biology · doi:10.1242/jeb.201.8.1153 · Cited by 368
Erythropoietin after a century of research: younger than ever
JELKMANN, W. E. B. (2007) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2007.00818.x · Cited by 372
Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)
McDonough, M. A., Li, V., Flashman, E., Chowdhury, R., Mohr, C., Liénard, B. M. R., Zondlo, J., Oldham, N. J., Clifton, I. J., Lewis, J. K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601283103 · Cited by 370
The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy
Albadari, N. G., Deng, S., & Li, W. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1613370 · Cited by 365
Regulation of the Erythropoietin Gene
Ebert, B. L., & Bunn, H. F. (1999) · Blood · doi:10.1182/blood.v94.6.1864 · Cited by 338
Mitochondrial reactive oxygen species regulate hypoxic signaling
Hamanaka, R. B., & Chandel, N. S. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.005 · Cited by 332
A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis
Percy, M. J., Zhao, Q., Flores, A., Harrison, C., Lappin, T. R. J., Maxwell, P. H., McMullin, M. F., & Lee, F. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508423103 · Cited by 330
Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation
Le, N. T. V., & Richardson, D. R. (2004) · Blood · doi:10.1182/blood-2004-05-1866 · Cited by 321
Hypoxic Regulation of Inducible Nitric Oxide Synthase via Hypoxia Inducible Factor-1 in Cardiac Myocytes
Jung, F., Palmer, L. A., Zhou, N., & Johns, R. A. (2000) · Circulation Research · doi:10.1161/01.res.86.3.319 · Cited by 317
HIF Inhibitors: Status of Current Clinical Development
Fallah, J., & Rini, B. I. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0752-z · Cited by 308
The tumor microenvironment and metastatic disease
Lunt, S. J., Chaudary, N., & Hill, R. P. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9182-2 · Cited by 303
Regulation of the Erythropoietin Gene
Imagawa, S., Goldberg, M. A., & Bunn, H. F. (1989) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0623-8_9 · Cited by 298
Regulation of the erythropoietin gene
Blanchard, K. L., Fandrey, J., Goldberg, M. A., & Bunn, H. F. (1993) · Stem Cells · doi:10.1002/stem.5530110604 · Cited by 297
Bioluminescence imaging: progress and applications
Badr, C. E., & Tannous, B. A. (2011) · Trends in biotechnology · doi:10.1016/j.tibtech.2011.06.010 · Cited by 293
Up-down regulation of HIF-1α in cancer progression
Rashid, M., Zadeh, L. R., Baradaran, B., Molavi, O., Ghesmati, Z., Sabzichi, M., & Ramezani, F. (2021) · Gene · doi:10.1016/j.gene.2021.145796 · Cited by 302
Hypoxic induction of Ctgf is directly mediated by Hif-1
Higgins, D. F., Biju, M. P., Akai, Y., Wutz, A., Johnson, R. S., & Haase, V. H. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00245.2004 · Cited by 284
Fibroblast growth factors-5 and -9 distinctly regulate expression and function of the gap junction protein connexin43 in cultured astroglial cells from different brain regions
Reuß, B., Hertel, M., Werner, S., & Unsicker, K. (2000) · Glia · doi:10.1002/(sici)1098-1136(200005)30:3 · Cited by 52
Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression
Fang, J. S., Gillies, R. D., & Gatenby, R. A. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.03.011 · Cited by 284
Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency
Mukhopadhyay, C. K., Mazumder, B., & Fox, P. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000636200 · Cited by 274
Crucial players in glycolysis: Cancer progress
Abbaszadeh, Z., Çeşmeli, S., & Avcı, Ç. B. (2019) · Gene · doi:10.1016/j.gene.2019.144158 · Cited by 274
Regulation of Angiogenesis by Hypoxia and Hypoxia‐Inducible Factors
Hickey, M. M., & Simon, M. C. (2006) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)76007-0 · Cited by 273
The molecular mechanism of erythropoietin action
Koury, M. J., & Bondurant, M. C. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb17466.x · Cited by 265
Development of a hypoxia-responsive vector for tumor-specific gene therapy
Shibata, T., Giaccia, A. J., & Brown, J. M. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301124 · Cited by 267
Regulation of Hypoxia-induced Pulmonary Hypertension by Vascular Smooth Muscle Hypoxia-Inducible Factor-1α
Ball, M. K., Waypa, G. B., Mungai, P. T., Nielsen, J. M., Czech, L., Dudley, V. J., Beussink‐Nelson, L., Dettman, R. W., Berkelhamer, S. K., Steinhorn, R. H., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201302-0302oc · Cited by 267
Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins
Takeda, K., Aguila, H. L., Parikh, N. S., Li, X., Lamothe, K., Duan, L.-J., Takeda, H., Lee, F. S., & Fong, G.-H. (2008) · Blood · doi:10.1182/blood-2007-09-114561 · Cited by 263
Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents
Richardson, D. R., Kalinowski, D. S., Lau, S. L., Jansson, P. J., & Lovejoy, D. B. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.04.003 · Cited by 260
Mechanisms Modulating Skeletal Muscle Phenotype
Blaauw, B., Schiaffino, S., & Reggiani, C. (2013) · Comprehensive physiology · doi:10.1002/cphy.c130009 · Cited by 298
Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene.
Pugh, C. W., Tan, C., Jones, R. W., & Ratcliffe, P. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10553 · Cited by 255
Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing
Webb, J. D., Coleman, M. L., & Pugh, C. W. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0147-7 · Cited by 261
Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets
Zhao, Y., Xiong, W., Li, C., Zhao, R., Lu, H., Song, S., Zhou, Y., Hu, Y., Shi, B., & Ge, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01652-9 · Cited by 275
HIF-1 in cancer therapy: two decade long story of a transcription factor
Soni, S., & Padwad, Y. S. (2017) · Acta Oncologica · doi:10.1080/0284186x.2017.1301680 · Cited by 251
“Studies on the molecular mechanisms of hematopoietic growth hormone erythropoietin (EPO) induction, the most salient response to hypoxia, set the course for recognition of HIF-1 which operates ubiquitously in mammalian cells [3].”
Background
Hypoxia-Inducible Factors and Cancer
Jun, J. C., Rathore, A., Younas, H., Gilkes, D., & Polotsky, V. Y. (2017) · Current Sleep Medicine Reports · doi:10.1007/s40675-017-0062-7 · Cited by 248
Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice.
Semenza, G. L., Koury, S. T., Nejfelt, M. K., Gearhart, J. D., & Antonarakis, S. E. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.19.8725 · Cited by 248
Self-citation
Erythropoietin.
Bunn, H. F. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011619 · Cited by 234
Targeting hypoxia-inducible factors: therapeutic opportunities and challenges
Yuan, X., Ruan, W., Bobrow, B., Carmeliet, P., & Eltzschig, H. K. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00848-6 · Cited by 245
Hypoxic preconditioning protects against ischemic brain injury
Sharp, F. R., Ran, R., Lu, A., Tang, Y., Strauss, K. I., Glass, T. F., Ardizzone, T. D., & Bernaudin, M. (2004) · NeuroRx · doi:10.1602/neurorx.1.1.26 · Cited by 242
Coordinate Regulation of the Oxygen-Dependent Degradation Domains of Hypoxia-Inducible Factor 1α
Chan, D. A., Sutphin, P. D., Yen, S., & Giaccia, A. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6415-6426.2005 · Cited by 248
Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates
Hewitson, K. S., Liénard, B. M. R., McDonough, M. A., Clifton, I. J., Butler, D., Soares, A. S., Oldham, N. J., McNeill, L. A., & Schofield, C. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608337200 · Cited by 235
HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner
Scortegagna, M., Ding, K., Zhang, Q., Oktay, Y., Bennett, M. J., Bennett, M., Shelton, J. M., Richardson, J. A., Moe, O. W., & Garcia, J. A. (2004) · Blood · doi:10.1182/blood-2004-05-1695 · Cited by 237
aHIF: a Natural Antisense Transcript Overexpressed in Human Renal Cancer and During Hypoxia
Thrash-Bingham, C., & Tartof, K. D. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.2.143 · Cited by 226
Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis
Semenza, G. L. (2009) · Blood · doi:10.1182/blood-2009-05-189985 · Cited by 228
Self-citation
Identification of Functional Hypoxia Response Elements in the Promoter Region of the DEC1 and DEC2 Genes
Miyazaki, K., Kawamoto, T., Tanimoto, K., Nishiyama, M., Honda, H., & Kato, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204938200 · Cited by 227
HIF at a glance
Brahimi-Horn, M. C., & Pouysségur, J. (2009) · Journal of Cell Science · doi:10.1242/jcs.035022 · Cited by 236
Regulatory mechanisms of hypoxia‐inducible factor 1 activity: Two decades of knowledge
Koyasu, S., Kobayashi, M., Gotö, Y., Hiraoka, M., & Harada, H. (2017) · Cancer Science · doi:10.1111/cas.13483 · Cited by 233
The transcription factors ATF-1 and CREB-1 bind constitutively to the hypoxia-inducible factor-1 (HIF-1)DNA recognition site
Kvietikova, I., Wenger, R. H., Marti, H. H., & Gassmann, M. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.22.4542 · Cited by 213

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 › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks