ArticleEndocrinology2016
Liganded Thyroid Hormone Receptors Transactivate the DNA Methyltransferase 3a Gene in Mouse Neuronal Cells.
Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Epigenetic Changes Associated With Obesity-related Metabolic Comorbidities.Journal of the Endocrine Society · 2025Review
- ExploringReports of biochemistry & molecular biology · 2025Article
- The Thyroid Hormone Analog GC-1 Mitigates Acute Lung Injury by Inhibiting M1 Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Thyroid hormone links environmental signals to DNA methylation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review.Nutrients · 2023Article
- Epigenetic developmental programming and intergenerational effects of thyroid hormones.Vitamins and hormones · 2023Review
- Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate Central Nervous System.BMC genomics · 2022Article
- Article
- Review
- Stress hormones mediate developmental plasticity in vertebrates with complex life cycles.Neurobiology of stress · 2021Article
- Thyroid Hormone Induces DNA Demethylation in Xenopus Tadpole Brain.Endocrinology · 2020Article
- Early life variations in temperature exposure affect the epigenetic regulation of the paraventricular nucleus in female rat pups.Proceedings. Biological sciences · 2020Article
- Topical L-thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy?Experimental dermatology · 2020Review
- DNA methylation dynamics underlie metamorphic gene regulation programs in Xenopus tadpole brain.Developmental biology · 2020Article
- Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.Molecular psychiatry · 2020Article
- Evidence for Prenatal Exposure to Thyroid Disruptors and Adverse Effects on Brain Development.European thyroid journal · 2019Review
- Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches.Environmental health perspectives · 2019Article
- Cognition-Enhancing Vagus Nerve Stimulation Alters the Epigenetic Landscape.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Transport, Metabolism, and Function of Thyroid Hormones in the Developing Mammalian Brain.Frontiers in endocrinology · 2019Review
- Novel Insight Into the Epigenetic and Post-transcriptional Control of Cardiac Gene Expression by Thyroid Hormone.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Thyroid hormone (T3) is essential for proper neurological development. The hormone, bound to its receptors, regulates gene transcription in part by modulating posttranslational modifications of histones. Methylation of DNA, which is established by the de novo DNA methyltransferase (DNMT)3a and DNMT3b, and maintained by DNMT1 is another epigenetic modification influencing gene transcription. The expression of Dnmt3a, but not other Dnmt genes, increases in mouse brain in parallel with the postnatal rise in plasma [T3]. We found that treatment of the mouse neuroblastoma cell line Neuro2a[TRβ1] with T3 caused rapid induction of Dnmt3a mRNA, which was resistant to protein synthesis inhibition, supporting that it is a direct T3-response gene. Injection of T3 into postnatal day 6 mice increased Dnmt3a mRNA in the brain by 1 hour. Analysis of two chromatin immunoprecipitation-sequencing datasets, and targeted analyses using chromatin immunoprecipitation, transfection-reporter assays, and in vitro DNA binding identified 2 functional T3-response elements (TREs) at the mouse Dnmt3a locus located +30.3 and +49.3 kb from the transcription start site. Thyroid hormone receptors associated with both of these regions in mouse brain chromatin, but with only 1 (+30.3 kb) in Neuro2a[TRβ1] cells. Deletion of the +30.3-kb TRE using CRISPR/Cas9 genome editing eliminated or strongly reduced the Dnmt3a mRNA response to T3. Bioinformatics analysis showed that both TREs are highly conserved among eutherian mammals. Thyroid regulation of Dnmt3a may be an evolutionarily conserved mechanism for modulating global changes in DNA methylation during postnatal neurological development.
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