@article{3922,
  keywords = {Repressor Proteins, Humans, Transcription Factors, Models, Molecular, Protein Conformation, HEK293 Cells, Chromosomal Proteins, Non-Histone, Cell Line, Tumor, Proto-Oncogene Proteins, Histones, Nucleosomes, Ubiquitination, Neoplasm Proteins, Oncogene Proteins, Fusion, Sarcoma, Synovial, Ubiquitins},
  author = {Matthew McBride and Nazar Mashtalir and Evan Winter and Hai Dao and Martin Filipovski and Andrew D{\textquoteright}Avino and Hyuk-Soo Seo and Neil Umbreit and Roodolph St Pierre and Alfredo Valencia and Kristin Qian and Hayley Zullow and Jacob Jaffe and Sirano Dhe-Paganon and Tom Muir and Cigall Kadoch},
  title = {The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma.},
  abstract = { <p>Interactions between chromatin-associated proteins and the histone landscape play major roles in dictating genome topology and gene expression. Cancer-specific fusion oncoproteins, which display unique chromatin localization patterns, often lack classical DNA-binding domains, presenting challenges in identifying mechanisms governing their site-specific chromatin targeting and function. Here we identify a minimal region of the human SS18-SSX fusion oncoprotein (the hallmark driver of synovial sarcoma) that mediates a direct interaction between the mSWI/SNF complex and the nucleosome acidic patch. This binding results in altered mSWI/SNF composition and nucleosome engagement, driving cancer-specific mSWI/SNF complex targeting and gene expression. Furthermore, the C-terminal region of SSX confers preferential affinity to repressed, H2AK119Ub-marked nucleosomes, underlying the selective targeting to polycomb-marked genomic regions and synovial sarcoma-specific dependency on PRC1 function. Together, our results describe a functional interplay between a key nucleosome binding hub and a histone modification that underlies the disease-specific recruitment of a major chromatin remodeling complex.</p> },
  year = {2020},
  journal = {Nat Struct Mol Biol},
  volume = {27},
  pages = {836-845},
  month = {2020 Sep},
  issn = {1545-9985},
  doi = {10.1038/s41594-020-0466-9},
  language = {eng},
}