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Publication

The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.

Cancer cell | 2018

Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

Pubmed ID: 29861296 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: DP2 CA195762
  • Agency: NCI NIH HHS, United States
    Id: R01 CA237241
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM095450

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

Paired Box Gene 3 (Waardenburg Syndrome-1) (antibody)

RRID:AB_2159398

This monoclonal targets ND

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c-Myc antibody [Y69] (antibody)

RRID:AB_731658

This monoclonal targets c-Myc antibody [Y69]

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Sox2 (D6D9) XP Rabbit mAb (antibody)

RRID:AB_2195767

This monoclonal targets Sox2

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Normal Rabbit IgG (antibody)

RRID:AB_1031062

This isotype control targets not applicable

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V5-Tag (D3H8Q) Rabbit Antibody (antibody)

RRID:AB_2687461

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H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

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Rabbit Anti-Histone H3, trimethyl (Lys27) Polyclonal antibody, Unconjugated (antibody)

RRID:AB_310624

This polyclonal targets Histone H3, trimethyl (Lys27)

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Anti-trimethyl-Histone H3 (Lys4), clone 15-10C-E4, Recombinant (antibody)

RRID:AB_1587134

This monoclonal targets Human Histone H3, trimethyl (Lys4)

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Anti-GAPDH Antibody (G-9) (antibody)

RRID:AB_10847862

This monoclonal targets GAPDH

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SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

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H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

ARID1A/BAF250 Antibody (antibody)

RRID:AB_2060365

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BAF200 (E-3) (antibody)

RRID:AB_2060382

This monoclonal targets BAF200 (E-3)

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Anti-ARID1A Antibody (C-7) (antibody)

RRID:AB_10917727

This monoclonal targets ARID1A

View all literature mentions

BAF47 (antibody)

RRID:AB_2191717

This monoclonal targets Smarcb1

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SS18 (D6I4Z) (antibody)

RRID:AB_2728667

This monoclonal targets SS18

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BAF155 (H-76) (antibody)

RRID:AB_2191997

This polyclonal targets BAF155 (H-76)

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Mouse Anti-Ini1 Monoclonal Antibody, Unconjugated (antibody)

RRID:AB_2270651

This monoclonal targets SMARCB1

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Brg-1 (G-7) (antibody)

RRID:AB_626762

This monoclonal targets SMARCA4

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Brg1 (D1Q7F) (antibody)

RRID:AB_2728743

This monoclonal targets Brg1

View all literature mentions

PAX7 (antibody)

RRID:AB_2299243

This monoclonal targets PAX7

View all literature mentions

Pol II antibody (antibody)

RRID:AB_2728744

This monoclonal targets Pol II

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V5 Tag Monoclonal Antibody (SV5-Pk1) (antibody)

RRID:AB_2556564

This monoclonal targets V5 Tag

View all literature mentions

Paired Box Gene 3 (Waardenburg Syndrome-1) (antibody)

RRID:AB_2159398

This monoclonal targets ND

View all literature mentions

Sox2 (D6D9) XP Rabbit mAb (antibody)

RRID:AB_2195767

This monoclonal targets Sox2

View all literature mentions

c-Myc antibody [Y69] (antibody)

RRID:AB_731658

This monoclonal targets c-Myc antibody [Y69]

View all literature mentions

Normal Rabbit IgG (antibody)

RRID:AB_1031062

This isotype control targets not applicable

View all literature mentions

V5-Tag (D3H8Q) Rabbit Antibody (antibody)

RRID:AB_2687461

This monoclonal targets V5-Tag

View all literature mentions

Anti-GAPDH Antibody (G-9) (antibody)

RRID:AB_10847862

This monoclonal targets GAPDH

View all literature mentions

H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

View all literature mentions

Anti-trimethyl-Histone H3 (Lys4), clone 15-10C-E4, Recombinant (antibody)

RRID:AB_1587134

This monoclonal targets Human Histone H3, trimethyl (Lys4)

View all literature mentions

Rabbit Anti-Histone H3, trimethyl (Lys27) Polyclonal antibody, Unconjugated (antibody)

RRID:AB_310624

This polyclonal targets Histone H3, trimethyl (Lys27)

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

View all literature mentions

BAF200 (E-3) (antibody)

RRID:AB_2060382

This monoclonal targets BAF200 (E-3)

View all literature mentions

ARID1A/BAF250 Antibody (antibody)

RRID:AB_2060365

This unknown targets ARID1A/BAF250

View all literature mentions

Anti-ARID1A Antibody (C-7) (antibody)

RRID:AB_10917727

This monoclonal targets ARID1A

View all literature mentions

SS18 (D6I4Z) (antibody)

RRID:AB_2728667

This monoclonal targets SS18

View all literature mentions

BAF155 (H-76) (antibody)

RRID:AB_2191997

This polyclonal targets BAF155 (H-76)

View all literature mentions

BAF47 (antibody)

RRID:AB_2191717

This monoclonal targets Smarcb1

View all literature mentions

Mouse Anti-Ini1 Monoclonal Antibody, Unconjugated (antibody)

RRID:AB_2270651

This monoclonal targets SMARCB1

View all literature mentions

Brg1 (D1Q7F) (antibody)

RRID:AB_2728743

This monoclonal targets Brg1

View all literature mentions

Brg-1 (G-7) (antibody)

RRID:AB_626762

This monoclonal targets SMARCA4

View all literature mentions

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