RNA reinforces condensate nucleation on chromatin to amplify oncogenic transcription - PubMed
3 hours ago
- #ENL-RNA interaction
- #oncogenic condensates
- #chromatin transcription
- Mutant ENL chromatin reader drives oncogenesis by forming condensates at specific target sites.
- Locally produced RNA reinforces mutant ENL condensate nucleation, chromatin binding, and oncogenic activity.
- RNA binding occurs via a basic patch in the YEATS domain of ENL, enhancing condensate formation in vitro and in cells.
- Blocking ENL-RNA interactions or transcription impairs condensate reformation at endogenous targets.
- RNA binding increases mutant ENL occupancy and transcriptional bursting at loci permissive for condensates.
- Disrupting RNA binding in mouse models suppresses mutant ENL-driven oncogenic transcription and leukemogenesis.
- The study reveals how oncogenic proteins hijack local transcripts to reinforce condensate nucleation and promote tumorigenesis.