The European Zebrafish Society was formed as a successor of "EuFishBioMed e.V." to foster zebrafish research, providing a platform for researchers and a framewokr for grant funding for young researche...

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

Synovial sarcoma is driven by the SS18-SSX fusion oncoprotein, which has been assumed to promote tumorigenesis through its incorporation into the SWI/SNF chromatin remodeling complexes. Accordingly, therapeutic efforts have focused on targeting SS18-SSX containing SWI/SNF assemblies, yet these approaches have produced limited clinical benefit. Here, we demonstrate that SS18-SSX sustains oncogenic transcription independent of SWI/SNF activity. Despite efficient degradation and dismantling of SWI/SNF complexes, fusion occupancy at target loci and associated gene expression programs remain largely intact. Instead, we identify the acetyltransferase P300 as an essential co-factor supporting SS18-SSX chromatin binding and transcriptional activation. Targeting P300 displaces the fusion from chromatin, suppresses its transcriptional output, compromising synovial sarcoma viability. Notably, dual PROTAC mediated degradation of P300 and SWI/SNF produces strong synergistic effects, broadly disrupting SS18-SSX localization and function. These findings redefine the mechanistic basis of synovial sarcoma and reveal a mechanistically anchored therapeutic strategy for targeting its core oncogenic driver. ### Competing Interest Statement C.R.V. has been a consultant for Flare Therapeutics, Roivant Sciences and C4 Therapeutics; has served on the advisory boards of KSQ Therapeutics, Syros Pharmaceuticals and Treeline Biosciences; has received research funding from Boehringer Ingelheim and Treeline Biosciences; and owns stock in Treeline Biosciences. S.A.A. has been a consultant and/or shareholder for Neomorph, Imago Biosciences, Hyku Therapeutics, C4 Therapeutics, Accent Therapeutics and Nimbus Therapeutics; and has received research support from Janssen and Syndax. N.O.C. is a co-founder, shareholder and management consultant for PhenoTherapeutics Ltd; and a shareholder in Amplia Therapeutics Ltd All other authors declare no financial interests UKRI, EP/X039633/1 Worldwide Cancer Research, https://ror.org/031tfbz57, 21-0271 Science Foundation Ireland, https://ror.org/0271asj38, 18/SIRG/5573

Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and s...

PhD Project - EASTBIO - Dissecting CIC::DUX4 oncogenic circuitry through single-cell perturbation profiling and network inference at University of Edinburgh, listed on FindAPhD.com

We’ve made Affinity completely free, empowering professional designers with studio-grade creative software, supported by Canva’s sustainable ecosystem.

Developmental enhancers are central regulatory elements that can activate multiple genes, yet how they selectively regulate one gene over its neighbours remains unclear. Using the Drosophila twist E3 ...

Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...