We also show that an oncogenic fusion protein can drive compartment formation identifying an additional modality by which chromosome folding is compromised in cancer. In summary, we provide empirical evidence that 'like attracts like' chromatin interactions result in nuclear compartment formation. However, transcription is not required to maintain chromatin contacts within the compartment and contacts between newly acetylated regions are formed after inhibiting RNA polymerase II initiation.

Genes within the BRD4-NUT-driven compartment are highly transcribed. We also find that degradation of bromo- and extraterminal domain (BET) proteins by a small-molecule proteolysis targeting chimera (PROTAC) results in collapse of the BRD4-NUT-driven nuclear compartment. Intra-compartment interactions are exceptionally strong for the BRD4-NUT-driven nuclear compartment much more so than any of the other previously identified nuclear compartments. Domain-domain contacts occur both within and between chromosomes forming a BRD4-NUT-driven nuclear compartment. We find long-range chromatin interactions spanning tens to hundreds of megabases between hyperacetylated chromatin domains. BRD4-NUT, the fusion oncoprotein causal for NUT carcinoma, forms broad hyperacetylated domains of chromatin. Title: Nuclear Compartment Formation by an Oncogenic Fusion ProteinĬhromosome compartments are important features of nuclear organization but have an unclear mechanism of formation and indeterminate functional significance. Please join us for the next NIPM Seminar on Thursday, February 23, 2023, from noon - 1:30 pm with Kyle Eagen, Ph.D., assistant professor, Baylor College of Medicine

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