Title | The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | McBride MJ, Mashtalir N, Winter EB, Dao HT, Filipovski M, D'Avino AR, Seo H-S, Umbreit NT, St Pierre R, Valencia AM, Qian K, Zullow HJ, Jaffe JD, Dhe-Paganon S, Muir TW, Kadoch C |
Journal | Nat Struct Mol Biol |
Date Published | 2020 Aug 03 |
ISSN | 1545-9985 |
Abstract | 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. |
DOI | 10.1038/s41594-020-0466-9 |
Alternate Journal | Nat. Struct. Mol. Biol. |
PubMed ID | 32747783 |
Submitted by bel2021 on August 25, 2020 - 10:48am