The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma.
Nat Struct Mol Biol
; 27(9): 836-845, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32747783
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
/
Proteínas Cromossômicas não Histona
/
Histonas
/
Ubiquitinas
/
Proteínas de Fusão Oncogênica
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Proteínas Proto-Oncogênicas
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Sarcoma Sinovial
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article