ArticleGenes & development2001
A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 92 citations in OpenAlex.
- Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.Blood advances · 2024Article
- Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium-glucose cotransporter 2 inhibitors.European heart journal · 2023Article
- Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia.BMC genomics · 2023Observational
- Hepatocyte Nuclear Factor 4α (HNF4α) Plays a Controlling Role in Expression of the Retinoic Acid Receptor β (International journal of molecular sciences · 2023Article
- Selective HepaticInternational journal of molecular sciences · 2023Article
- Defects in placental syncytiotrophoblast cells are a common cause of developmental heart disease.Nature communications · 2023Article
- The transcription factor HNF-4α: a key player in haematological disorders.Archives of medical science : AMS · 2023Article
- Vitamin A: too good to be bad?Frontiers in pharmacology · 2023Review
- Role of Nuclear Receptors in Controlling Erythropoiesis.International journal of molecular sciences · 2022Review
- Review
- Review
- Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis.International journal of molecular sciences · 2021Review
- Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.Scientific reports · 2021Article
- Phases and Mechanisms of Embryonic Cardiomyocyte Proliferation and Ventricular Wall Morphogenesis.Pediatric cardiology · 2019Review
- Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
- Endogenous retinoid X receptor ligands in mouse hematopoietic cells.Science signaling · 2017Article
- Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism.International journal of molecular sciences · 2015Review
- Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion.Cardiovascular research · 2015Article
- Mechanisms of retinoic acid signalling and its roles in organ and limb development.Nature reviews. Molecular cell biology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The cytokine erythropoietin (Epo) promotes erythropoietic progenitor cell proliferation and is required for erythropoietic differentiation. We have found that the Epo gene is a direct transcriptional target gene of retinoic acid signaling during early erythropoiesis (prior to embryonic day E12.5) in the fetal liver. Mouse embryos lacking the retinoic acid receptor gene RXR alpha have a morphological and histological phenotype that is comparable with embryos in which the Epo gene itself has been mutated, and flow cytometric analysis indicates that RXR alpha-deficient embryos are deficient in erythroid differentiation. Epo mRNA levels are reduced substantially in the fetal livers of RXR alpha(-/-) embryos at E10.25 and E11.25, and genetic analysis shows that the RXR alpha and Epo genes are coupled in the same pathway. We furthermore show that the Epo gene is retinoic acid inducible in embryos, and that the Epo gene enhancer contains a DR2 sequence that represents a retinoic acid receptor-binding site and a retinoic acid receptor transcriptional response element. However, unlike Epo-deficient embryos that die from anemia, the erythropoietic deficiency in RXR alpha(-/-) embryos is transient; Epo mRNA is expressed at normal levels by E12.5, and erythropoiesis and liver morphology are normal by E14.5. We show that HNF4, like RXR alpha a member of the nuclear receptor family, is abundantly expressed in fetal liver hepatocytes, and is competitive with retinoic acid receptors for occupancy of the Epo gene enhancer DR2 element. We propose that Epo expression is regulated during the E9.5--E11.5 phase of fetal liver erythropoiesis by RXR alpha and retinoic acid, and that expression then becomes dominated by HNF4 activity from E11.5 onward. This transition may be responsible for switching regulation of Epo expression from retinoic acid control to hypoxic control, as is found throughout the remainder of life.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.