Projects per year
Abstract
The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned—ensuring precise gene expression and developmental fidelity—remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound TETOGT–PROSER1–DBHS (TOPD) complexes, which regulate DNAdemethylation and developmental gene expression. Surprisingly, we found that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element derepression. Our findings identify PROSER1 as a key factor that both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.
Original language | English |
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Pages (from-to) | 952-964 |
Number of pages | 13 |
Journal | Genes & Development |
DOIs | |
Publication status | Published - Dec 2024 |
Keywords
- TET1
- TET2
- TET3
- DNA methylation
- TOPD
- development
- neurodevelopmental disorder
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Dive into the research topics of 'PROSER1 modulates DNA demethylation through dual mechanisms to prevent syndromic developmental malformations'. Together they form a unique fingerprint.Projects
- 1 Active
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Aberrant DNA Methylation and its Impact in Blood Cancer Development (Career Development Fellowship)
Owen-Hughes, T. (Investigator) & Rasmussen, K. (Investigator)
1/06/19 → 31/05/25
Project: Research
Research output
- 1 Preprint
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PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations
Fleming, A., Knatko, E. V., Li, X., Zoch, A., Heckhausen, Z., Stransky, S., Brenes Murillo, A., Sidoli, S., Hajkova, P., O'Carroll, D. & Rasmussen, K. (Lead / Corresponding author), 2 Aug 2024, BioRxiv, 34 p.Research output: Working paper/Preprint › Preprint
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