Molecular basis for the inhibition of de novo DNA methylation by TCL1A - PubMed
5 days ago
- #DNMT3A
- #TCL1A
- #DNA methylation
- DNMT3A/B are essential for de novo DNA methylation, impacting embryonic development and cell fate.
- TCL1A plays a dual role: critical in embryogenesis but promotes lymphomagenesis when deregulated.
- The cryo-EM structure reveals DNMT3A-TCL1A complex formation, with TCL1A binding to DNMT3A's catalytic domain.
- TCL1A induces conformational changes in DNMT3A, reducing DNA accessibility and blocking methyltransferase activity.
- Biochemical assays and simulations support a dynamic inhibition mechanism by TCL1A to suppress DNA methylation.