ArticleNucleic acids research2020
Phosphorylation of Tet3 by cdk5 is critical for robust activation of BRN2 during neuronal differentiation.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Housing environment bilaterally alters transcriptomic profile in the rat hippocampal CA1 region.PloS one · 2025Article
- The Function of H2A Histone Variants and Their Roles in Diseases.Biomolecules · 2024Review
- Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Vitamin C epigenetically controls osteogenesis and bone mineralization.Nature communications · 2022Article
- Truncated Tau caused by intron retention is enriched in Alzheimer's disease cortex and exhibits altered biochemical properties.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms that regulate the activities of TET proteins.Cellular and molecular life sciences : CMLS · 2022Review
- The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.Cell & bioscience · 2022Review
- The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome.Epigenetics · 2022Article
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Downregulation of the FTO mNature cancer · 2021Article
- TET3 regulates DNA hydroxymethylation of neuroprotective genes following focal ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection.Frontiers in immunology · 2021Review
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tet3 regulates the dynamic balance between 5-methylcyotsine (5mC) and 5-hydroxymethylcytosine (5hmC) in DNA during brain development and homeostasis. However, it remains unclear how its functions are modulated in a context-dependent manner during neuronal differentiation. Here, we show that cyclin-dependent kinase 5 (cdk5) phosphorylates Tet3 at the highly conserved serine 1310 and 1379 residues within its catalytic domain, changing its in vitro dioxygenase activity. Interestingly, when stably expressed in Tet1, 2, 3 triple-knockout mouse embryonic stem cells (ESCs), wild-type Tet3 induces higher level of 5hmC and concomitant expression of genes associated with neurogenesis whereas phosphor-mutant (S1310A/S1379A) Tet3 causes elevated 5hmC and expression of genes that are linked to metabolic processes. Consistent with this observation, Tet3-knockout mouse ESCs rescued with wild-type Tet3 have higher level of 5hmC at the promoter of neuron-specific gene BRN2 when compared to cells that expressed phosphor-mutant Tet3. Wild-type and phosphor-mutant Tet3 also exhibit differential binding affinity to histone variant H2A.Z. The differential 5hmC enrichment and H2A.Z occupancy at BRN2 promoter is correlated with higher gene expression and more efficient neuronal differentiation of ESCs that expressed wild-type Tet3. Taken together, our results suggest that cdk5-mediated phosphorylation of Tet3 is required for robust activation of neuronal differentiation program.
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