ArticleBlood advances2020
HIF-1 directly induces TET3 expression to enhance 5-hmC density and induce erythroid gene expression in hypoxia.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.Cell · 2025Article
- Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways.Molecular medicine (Cambridge, Mass.) · 2025Review
- Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome.Nature communications · 2025Article
- PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis.eLife · 2024Article
- TET2 mutation as prototypic clonal hematopoiesis lesion.Seminars in hematology · 2024Review
- Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.Clinical epigenetics · 2023Review
- A systematic study of HIF1A cofactors in hypoxic cancer cells.Scientific reports · 2022Article
- Role of TET dioxygenases in the regulation of both normal and pathological hematopoiesis.Journal of experimental & clinical cancer research : CR · 2022Review
- Physioxia-induced downregulation of Tet2 in hematopoietic stem cells contributes to enhanced self-renewal.Blood · 2022Article
- Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Epigenetic and post-transcriptional repression support metabolic suppression in chronically hypoxic goldfish.Scientific reports · 2022Article
- TET3 promotes AML growth and epigenetically regulates glucose metabolism and leukemic stem cell associated pathways.Leukemia · 2022Article
- From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy.International journal of molecular sciences · 2021Review
- Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia.Cancers · 2021Review
- Epigenetic modifiers in normal and aberrent erythropoeisis.Seminars in hematology · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In mammalian cells, cytosines found within cytosine guanine dinucleotides can be methylated to 5-methylcytosine (5-mC) by DNA methyltransferases and further oxidized by the Ten-eleven translocation dioxygenase (TET) enzymes to 5-hydroxymethylcytosine (5-hmC). We have previously shown that hematopoietic stem and progenitor cells (HSPCs) with TET2 mutations have aberrant 5-hmC distribution and less erythroid differentiation potential. However, these experiments were performed under standard tissue culture conditions with 21% oxygen (O2), whereas HSPCs in human bone marrow reside in ∼1% O2. Therefore, to model human erythropoiesis more accurately, we compared 5-hmC distribution and gene expression in hypoxic vs normoxic conditions. Despite TET enzymes having limited O2 as a substrate in hypoxia, 5-hmC peaks were more numerous and pronounced than in normoxia. Among the TET genes, TET3 was upregulated specifically in hypoxia. We identified 2 HIF-1 binding sites in TET3 by chromatin immunoprecipitation of HIF-1α followed by sequencing, and TET3 upregulation was abrogated with deletion of both sites, indicating that TET3 is a direct HIF-1 target. Finally, we showed that loss of one or both of these HIF-1 binding sites in K562 cells disrupted erythroid differentiation in hypoxia and lowered cell viability. This work provides a molecular link between O2 availability, epigenetic modification of chromatin, and erythroid differentiation.
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