Phase separation of DUX family proteins drives totipotent-like state via 3D genome reorganization and retrotransposon activation - PubMed
4 hours ago
- #totipotency
- #3D genome
- #phase separation
- Phase separation of DUX family proteins (mouse Dux and human DUX4) drives totipotency-like states.
- DUX proteins form liquid-liquid phase-separated (LLPS) condensates via conserved arginine residues in intrinsically disordered regions (IDRs).
- These condensates recruit CBP/p300 and CTCF to establish super-enhancers (SEs) at MERVL/MT2 loci, enabling H3K27ac deposition and chromatin accessibility.
- DUX-driven phase separation facilitates 3D genome reorganization, including enhancer-promoter loops and TAD boundary shifts.
- Disruption of LLPS (DUXR70A) abolishes SE assembly, transcriptional activation, and embryonic chimerism.
- Human DUX4 requires phase separation for myotoxic gene activation and cytotoxicity in FSHD models.
- The study links phase separation to transcriptional control and 3D genome remodeling in totipotency, with implications for developmental biology and disease therapy.