Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development
Open accessAbstract
Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.
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The Asn-Gua residue base pairing is analogous to the Arg-Gua pair in DNA-bound CXXC domain structures.
“The Asn-Gua residue base pairing is analogous to the Arg-Gua pair in the DNA-bound CXXC domain structures (9, 21).”
From Structural studies of SALL family protein zinc finger cluster domains in complex with DNA reveal preferential binding to an AATA tetranucleotide motif (2022) · cites this paper as [21]
The Results section on Tet3 CXXC–DNA crystal structures describes His90 hydrogen-bonding with guanine and compares Tet3 with CFP1, but does not describe an Asn–guanine interaction analogous to an Arg–guanine interaction. Searches for Asn–guanine and Arg–guanine pairing found no passage in our copy that addresses the claimed analogy; page numbers were unavailable. (LLM, conf=0.75)
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References 57 · Cited by 271
Research works printed but not linked: 26
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- Authors
- Xu, Y., Xu, C., Kato, A., Tempel, W., Abreu, J. G., Bian, C., Hu, Y., Hu, D., Zhao, B., Cerovina, T., Diao, J., Wu, F., He, H. H., Cui, Q., Clark, E., Ma, C., Barbara, A., Veenstra, G. J. C., Xu, G., Kaiser, U. B., Liu, X. S., Sugrue, S. P., He, X., Min, J., Kato, Y., & Shi, Y. G.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Toronto (CA)
- Florida State University (US)
- Fudan University (CN)
- Harvard University (US)
- Chinese Academy of Sciences (CN)
- Radboud University Nijmegen (NL)
- University of Florida (US)
- Boston Children's Hospital (US)
- Corresponding author
- Min, Jinrong
- Kato, Yoichi
- Shi, Yujiang Geno
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 151
- Issue
- 6
- Pages
- 1200-1213
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3705565
- OpenAlex
- W1978867062
- Cited by
- 271
- References
- 57
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 12 · 2023: 12 · 2022: 20 · 2021: 18 · 2020: 11 · 2019: 25 · 2018: 20 · 2017: 29 · 2016: 31 · 2015: 24 · 2014: 29 · 2013: 23
- FWCI
- 9.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, 06CH11357, DE-AC02-)
- Eli Lilly and Company
- Pfizer
- Brigham and Women's Hospital
- University of Chicago (DE-AC02-06CH11357)
- Ontario Innovation Trust
- Genome Canada
- Wellcome Trust (1097737)
- Ontario Genomics
- Ontario Genomics Institute
- Fudan University
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health (DE-AC02–06CH11357, GM078458)
- Intellectual and Developmental Disabilities Research Center
- National Eye Institute (P30EY021721, R01EY007883)
- National Institute of General Medical Sciences (GM074241, R01GM078458, GM-078458, R01GM074241, GM087641, R15GM087641)
- Biological and Environmental Research (DEAC0206CH11357)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, 06CH11357)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- TET3, CXXC domain, 5-hydroxymethylcytosine, DNA methylation, transcriptional regulation, eye development, neural development, Xenopus embryo, embryonic development, gene expression regulation
- MeSH terms
- Animals, DNA-Binding Proteins, Eye, Molecular Sequence Data, Promoter Regions, Genetic, Xenopus laevis, Protein Structure, Tertiary, Xenopus Proteins, Dioxygenases, Neurogenesis
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