Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression.

@article{Fandrey2004OxygendependentAT,
  title={Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression.},
  author={J. Fandrey},
  journal={American journal of physiology. Regulatory, integrative and comparative physiology},
  year={2004},
  volume={286 6},
  pages={
          R977-88
        }
}
  • J. Fandrey
  • Published 2004
  • Medicine, Biology
  • American journal of physiology. Regulatory, integrative and comparative physiology
Hypoxia-inducible expression of the gene encoding for the glycoprotein hormone erythropoietin (EPO) is the paradigm of oxygen-regulated gene expression. EPO is the main regulator of red blood cell production and more than 100 years of research on the regulation of EPO production have led to the identification of a widespread cellular oxygen sensing mechanism. Central to this signaling cascade is the transcription factor complex hypoxia-inducible factor-1 (HIF-1). Meanwhile, it is known that HIF… Expand
HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION
TLDR
In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene, and the HIF system is implicated in the pathophysiology of many human diseases. Expand
Nonrenal regulation of EPO synthesis.
TLDR
An overview of the molecular aspects ofEPO gene regulation by hypoxia-inducible transcription factors and of the tissue-specific regulation of EPO production in adult mammals is provided. Expand
Oxygen-regulated expression of the erythropoietin gene in the human renal cell line REPC.
TLDR
The human kidney cell line REPC (for renal Epo-producing cells), established from an explanted human kidney exhibiting EPO gene expression and release of the EPO protein in an oxygen-dependent manner, is presented for the first time. Expand
Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis
TLDR
Additional molecular mechanisms involved in the HIF-EPO pathway that correlate with erythropoiesis are investigated, including genes encoding transcription factors and proteins that control transcriptional activation or repression; genes encoding kinases, deacetylases, methyltransferases, conjugating enzymes, protein ligases, and proteases involved in post-translational modifications; and genes encoding nuclear transport receptors that regulate nuclear transport. Expand
Herpesvirus entry mediator regulates hypoxia-inducible factor-1α and erythropoiesis in mice.
TLDR
Signaling through herpesvirus entry mediator (HVEM), a molecule of the TNF receptor superfamily, promoted HIF-1α activity in the kidney and subsequently facilitated renal Epo production and erythropoiesis in vivo under normoxic conditions, suggesting this molecular mechanism could represent a therapeutic target for Epo-responsive diseases, including anemia. Expand
Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia.
TLDR
Evidence that hepatocyte-derived Hif-2 is involved in the regulation of iron metabolism genes is provided, supporting a role for HIF-2 in the coordination of EPO synthesis with iron homeostasis. Expand
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo.
TLDR
Conditional inactivation of Hif-2alpha in pVHL-deficient mice suppressed hepatic Epo and the development of polycythemia is shown, providing genetic evidence that HIF-1 and H IF-2 have distinct roles in the regulation of hypoxia-inducible genes and that EPO is preferentially regulated by HIFs in the liver. Expand
Oxygen-dependent Regulation of Transcription by the Hypoxia-inducible Factor-1
Under limited oxygen availability (hypoxia) cells undergo rapid reprogramming in order to survive in the new environment until normoxic conditions are re-established. The observation that hypoxia canExpand
List of contributors
Erythropoietin (EPO) is a glycoprotein hormone, which is produced in kidney and Hver, and is mainly involved in regulating proliferation and maturation of red blood cells. EPO gene expression isExpand
Hypoxic regulation of erythropoiesis and iron metabolism.
  • V. Haase
  • Biology, Medicine
  • American journal of physiology. Renal physiology
  • 2010
TLDR
Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review. Expand
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References

SHOWING 1-10 OF 172 REFERENCES
Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein.
TLDR
A model is proposed in which a ligand-dependent conformational change in a heme protein accounts for the mechanism by which hypoxia as well as cobalt and nickel stimulate the production of Epo. Expand
A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene.
TLDR
In Hep3B cells, clones modified to express HAF antisense RNA showed an attenuated response to hypoxia-mediated induction of both erythropoietin and vascular endothelial growth factor transcription. Expand
Hypoxic Regulation of Lactate Dehydrogenase A
TLDR
To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, the 5′ flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH) is studied. Expand
Expression of Hypoxia-Inducible Factor-1 and -2 in Hypoxic and Ischemic Rat Kidneys
Oxygen tensions in the kidney are heterogeneous, and their changes presumably play an important role in renal physiologic and pathophysiologic processes. A family of hypoxia-inducible transcriptionExpand
Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys.
TLDR
The kidney demonstrates a marked potential for upregulation of HIF, but accumulation of Hif-1alpha and HIF-2alpha is selective with respect to cell type, kidney zone, and experimental conditions, with the expression patterns partly matching known oxygen profiles. Expand
Hypoxia-inducible erythropoietin gene expression in human neuroblastoma cells.
TLDR
Two human neuroblastoma cell lines, SH-SY5Y and Kelly, may provide a new in vitro model for studying the mechanism of tissue-specific, hypoxia-inducible EPO gene expression. Expand
Inducible operation of the erythropoietin 3' enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism.
TLDR
It is shown that an oxygen-sensing system similar, or identical, to that controlling erythropoietin expression is wide-spread in mammalian cells and mediates other adaptive responses to hypoxia. Expand
Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus.
TLDR
Ovariectomized mice were given E(2) and/or exposed to hypoxia, and temporal patterns of Epo mRNA levels were examined, indicating that downregulation operates in the kidney but not in the brain. Expand
Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.
TLDR
It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme. Expand
Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation-free hypoxia-inducible factor-1 DNA-binding site.
TLDR
It is found that methylation of the HBS abolishes Hif-1 DNA binding as well as hypoxic reporter gene activation, suggesting that a methylation-free HBS is mandatory for HIF-1 function. Expand
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