ArticleNucleic acids research2018
Oxygen gradients can determine epigenetic asymmetry and cellular differentiation via differential regulation of Tet activity in embryonic stem cells.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Impacts of Oxygen Tension on Developmental Competence of Preimplantation Embryos.Biomolecules · 2026Review
- Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome.Nature communications · 2025Article
- The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.Frontiers in bioscience (Landmark edition) · 2025Review
- Tet1-mediated 5hmC regulates hippocampal neuroinflammation via wnt signaling as a novel mechanism in obstructive sleep apnoea leads to cognitive deficit.Journal of neuroinflammation · 2024Article
- Self-Organization of Long-Lasting Human Endothelial Capillary-Like Networks Guided by DLP Bioprinting.Advanced healthcare materials · 2024Article
- Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Article
- The interplay of cells, polymers, and vascularization in three-dimensional lung models and their applications in COVID-19 research and therapy.Stem cell research & therapy · 2023Review
- Oxygen availability influences the incidence of testicular teratoma inFrontiers in genetics · 2023Article
- Recent advances in understanding DNA methylation of prostate cancer.Frontiers in oncology · 2023Review
- Fetal oxygenation in the last weeks of pregnancy evaluated through the umbilical cord blood gas analysis.Frontiers in pediatrics · 2023Article
- Diphyodont tooth replacement of Brasilodon-A Late Triassic eucynodont that challenges the time of origin of mammals.Journal of anatomy · 2022Article
- Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids.Development (Cambridge, England) · 2022Article
- DNA Hypomethylation May Contribute to Metabolic Recovery of Frozen Wood Frog Brains.Epigenomes · 2022Article
- Spectroscopic and in vitro Investigations of FeChembiochem : a European journal of chemical biology · 2022Review
- NOS2 andProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Physoxia Influences Global and Gene-Specific Methylation in Pluripotent Stem Cells.International journal of molecular sciences · 2022Article
- Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment.Antioxidants (Basel, Switzerland) · 2022Review
- Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice.Epigenetics & chromatin · 2021Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Graded levels of molecular oxygen (O2) exist within developing mammalian embryos and can differentially regulate cellular specification pathways. During differentiation, cells acquire distinct epigenetic landscapes, which determine their function, however the mechanisms which regulate this are poorly understood. The demethylation of 5-methylcytosine (5mC) is achieved via successive oxidation reactions catalysed by the Ten-Eleven-Translocation (Tet) enzymes, yielding the 5-hydroxymethylcytosine (5hmC) intermediate. These require O2 as a co-factor, and hence may link epigenetic processes directly to O2 gradients during development. We demonstrate that the activities of Tet enzymes display distinct patterns of [O2]-dependency, and that Tet1 activity, specifically, is subject to differential regulation within a range of O2 which is physiologically relevant in embryogenesis. Further, differentiating embryonic stem cells displayed a transient burst of 5hmC, which was both dependent upon Tet1 and inhibited by low (1%) [O2]. A GC-rich promoter region within the Tet3 locus was identified as a significant target of this 5mC-hydroxylation. Further, this region was shown to associate with Tet1, and display the histone epigenetic marks, H3K4me3 and H3K27me3, which are characteristic of a bivalent, developmentally 'poised' promoter. We conclude that Tet1 activity, determined by [O2] may play a critical role in regulating cellular differentiation and fate in embryogenesis.
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Registered trials
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