The TDG protein environment connects active DNA demethylation with chromatin and RNA biology
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| Argitaratua izan da: | Cellular and Molecular Life Sciences vol. 83, no. 1 (Dec 2026), p. 15 |
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| Beste egile batzuk: | , , , , , , , , |
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Springer Nature B.V.
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| Sarrera elektronikoa: | Citation/Abstract Full Text Full Text - PDF |
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| 022 | |a 1420-682X | ||
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| 024 | 7 | |a 10.1007/s00018-025-05943-y |2 doi | |
| 035 | |a 3288173756 | ||
| 045 | 2 | |b d20261201 |b d20261231 | |
| 084 | |a 108381 |2 nlm | ||
| 100 | 1 | |a Richina, Federica |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 245 | 1 | |a The TDG protein environment connects active DNA demethylation with chromatin and RNA biology | |
| 260 | |b Springer Nature B.V. |c Dec 2026 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Understanding the interplay between DNA methylation and gene expression remains a challenge. This study explores the proteome of active DNA demethylation in murine embryonic stem cells (mESC), focusing on the base-excision-repair (BER) step initiated by the Thymine DNA Glycosylase (TDG). Using BioID2 proximity labeling, we identified a TDG interactome encompassing four functional aspects: chromatin organization and transcription, chromosomal organization, RNA processing, and ribosomal biogenesis. We show specifically that TDG participates in a genome regulatory network involving chromatin remodelers and modifiers such as RUVBL2 and the H3K4 methyltransferase complex tethering factor HCFC1, consistent with the dysregulation of histone modifications observed in TDG-deficient cells. We also identified the paraspeckle components PSPC1 and NONO as TDG interactors, implicating TDG in RNA-mediated nuclear processes. This led us to show that TDG is an RNA-binding protein, interacting with long-noncoding RNAs (lncRNA), including the paraspeckle organizing lncRNA Neat1, previously reported to target TET proteins to genomic sites and to engage in R-loop regulation. We then demonstrate TDG’s ability to excise oxidized 5-methylcytosine in RNA:DNA hybrids, suggesting a role of active DNA demethylation in the regulation of R-loops. Our findings thus unveil a direct crosstalk between active DNA demethylation, chromatin modification and remodeling as well as RNA-genome interactions in mESC, providing avenues for future mechanistic investigations. | |
| 653 | |a DNA methylation | ||
| 653 | |a rRNA | ||
| 653 | |a Embryo cells | ||
| 653 | |a Tethering | ||
| 653 | |a Methyltransferase | ||
| 653 | |a Thymine | ||
| 653 | |a Humidity | ||
| 653 | |a Histones | ||
| 653 | |a Ribonucleic acid--RNA | ||
| 653 | |a Stem cells | ||
| 653 | |a DNA glycosylase | ||
| 653 | |a Chromatin remodeling | ||
| 653 | |a Genomes | ||
| 653 | |a Non-coding RNA | ||
| 653 | |a Epigenetics | ||
| 653 | |a Hybrids | ||
| 653 | |a Demethylation | ||
| 653 | |a Proteins | ||
| 653 | |a Plasmids | ||
| 653 | |a Oxidation | ||
| 653 | |a Thymine DNA glycosylase | ||
| 653 | |a Functional morphology | ||
| 653 | |a Gene expression | ||
| 653 | |a RNA-binding protein | ||
| 653 | |a Cloning | ||
| 653 | |a Deoxyribonucleic acid--DNA | ||
| 653 | |a Proteomes | ||
| 653 | |a RNA processing | ||
| 653 | |a R-loops | ||
| 653 | |a Environmental | ||
| 700 | 1 | |a Noreen, Faiza |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); Swiss Institute of Bioinformatics, Basel, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) | |
| 700 | 1 | |a Bauer, Christina |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Weber, Alain |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Kunz, Christophe |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Buczak, Katarzyna |u University of Basel, Proteomics Facility Biozentrum, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Schwarz, Simon D. |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Wu, Fabian |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Schürmann, David |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 700 | 1 | |a Schär, Primo |u University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) | |
| 773 | 0 | |t Cellular and Molecular Life Sciences |g vol. 83, no. 1 (Dec 2026), p. 15 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3288173756/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3288173756/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3288173756/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |