TET3 Is Recruited by REST for Context-Specific Hydroxymethylation and Induction of Gene Expression
Open accessAbstract
Ten-eleven translocation hydroxylases (TET1-3) oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In neurons, increased 5hmC levels within gene bodies correlate positively with gene expression. The mechanisms controlling TET activity and 5hmC levels are poorly understood. In particular, it is not known how the neuronal TET3 isoform lacking a DNA-binding domain is targeted to the DNA. To identify factors binding to TET3, we screened for proteins that co-precipitate with TET3 from mouse retina and identified the transcriptional repressor REST as a highly enriched TET3-specific interactor. REST was able to enhance TET3 hydroxylase activity after co-expression and overexpression of TET3-activated transcription of REST target genes. Moreover, we found that TET3 also interacts with NSD3 and two other H3K36 methyltransferases and is able to induce H3K36 trimethylation. We propose a mechanism for transcriptional activation in neurons that involves REST-guided targeting of TET3 to the DNA for directed 5hmC generation and NSD3-mediated H3K36 trimethylation.
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The establishment and maintenance of patterns of histone and DNA modifications in a tissue-specific manner may be controlled by TFs directly or indirectly interacting with epigenetic modifiers, such as the histone acetylase CBP/p300.
“The establishment and maintenance of patterns of histone and DNA modifications in a tissue-specific manner may be controlled by TFs directly or indirectly interacting with epigenetic modifiers (21), such as the histone acetylase CBP/p300 (22).”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [21]
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Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · cited 2× · see citing works
“…in the (tri-) methylation of nucleosomal his- 290 Cell Reports 11, 283–294, April 14, 2015 ª2015 The Authors tone H3 at lysine 36 (H3K36), which is an epigenetic mark commonly associated with transcription of active chromatin (Bernstein et al., 2005; Heintzman et al., 2007; Kouzarides, 2007).”
BackgroundThe Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700 · see citing works
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419 · see citing works
Kulak, N. A., Pichler, G., Paron, I., Nagaraj, N., & Mann, M. (2014) · Nature Methods · doi:10.1038/nmeth.2834 · Cited by 1,719 · see citing works
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
Williams, K., Christensen, J., Pedersen, M. T., Johansen, J. V., Cloos, P. A. C., Rappsilber, J., & Helin, K. (2011) · Nature · doi:10.1038/nature10066 · Cited by 1,021 · see citing works
Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.004 · Cited by 973 · see citing works
Self-citationDynamic regulation of transcriptional states by chromatin and transcription factors
Voss, T. C., & Hager, G. L. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3623 · Cited by 504 · see citing works
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Research works printed but not linked: 2
- [1]1. Bernstein, B.E. ∙ Kamal, M. ∙ Lindblad-Toh, K. ... Genomic maps and comparative analysis of histone modifications in human and mouse Cell. 2005; 120:169-181 Full Text Full Text (PDF) Scopus (1228) PubMed Google Scholar
- [2]2. Chong, J.A. ∙ Tapia-Ramírez, J. ∙ Kim, S. ... REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons Cell. 1995; 80:949-957
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TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661 · see citing works
Jin, S.-G., Zhang, Z.-M., Dunwell, T. L., Harter, M. R., Wu, X., Johnson, J., Li, Z., Liu, J., Szabó, P. E., Lu, Q., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.044 · Cited by 138 · see citing works
Tet Enzymes, Variants, and Differential Effects on Function
Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., & Pnueli, L. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00022 · Cited by 130 · see citing works
Thakur, A., Wong, J. C. H., Wang, E. Y., Lotto, J., Kim, D., Cheng, J., Mingay, M., Cullum, R., Moudgil, V., Ahmed, N., et al. (2019) · Hepatology · doi:10.1002/hep.30631 · Cited by 75 · see citing works
- Authors
- Perera, A., Eisen, D., Wagner, M., Laube, S. K., Künzel, A. F., Koch, S., Steinbacher, J., Schulze, E., Splith, V., Mittermeier, N., Müller, M., Biel, M., Carell, T., & Michalakis, S.
- Affiliations
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Carell, Thomas
- Michalakis, Stylianos
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 11
- Issue
- 2
- Pages
- 283-294
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2019631798
- Cited by
- 145
- References
- 7
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 19 · 2018: 16 · 2017: 15 · 2016: 20 · 2015: 4
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (EXC114)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- TET3, rest, 5-hydroxymethylcytosine, DNA hydroxymethylation, 5-methylcytosine oxidation, NSD3, H3K36 trimethylation, transcriptional activation, neuronal gene expression, protein-protein interaction, retina
- MeSH terms
- RE1-Silencing Transcription Factor, Animals, Cytosine, DNA-Binding Proteins, Gene Expression Regulation, Neurons, Histone-Lysine N-Methyltransferase, Proto-Oncogene Proteins, Repressor Proteins, Retina, Transcriptional Activation, DNA Methylation, 5-Methylcytosine, Dioxygenases, Mice
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