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Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined Smarcb1 genetic loss with SS18-SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18-SSX alone, indicating a defining role for SMARCB1 in synovial sarcoma. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human synovial sarcoma cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, coincorporated with SS18-SSX in the latter. Recombinant expression of CBAF components in human cells reconstituted CBAF subcomplexes that contained equal levels of SMARCB1 regardless of SS18 or SS18-SSX inclusion. In vivo, SS18-SSX expression led to whole-complex CBAF degradation, rendering increases in the relative prevalence of other BAF-family subtypes, PBAF and GBAF complexes, over time. Thus, SS18-SSX alters BAF subtypes levels/balance and genome distribution, driving synovial sarcomagenesis. SIGNIFICANCE: The protein level of BAF component SMARCB1 is reduced in synovial sarcoma but plays a defining role, incorporating into PBAF and SS18-SSX-containing canonical BAF complexes. Reduced levels of SMARCB1 derive from whole-complex degradation of canonical BAF driven by SS18-SSX, with relative increases in the abundance of other BAF-family subtypes.See related commentary by Maxwell and Hargreaves, p. 2375.This article is highlighted in the In This Issue feature, p. 2355.
Pubmed ID: 34078620
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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets ARID1B
View all literature mentionsThis unknown targets BAF57/SMARCE1
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis unknown targets SMARCC1
View all literature mentionsThis monoclonal targets ARID1A/BAF250A
View all literature mentionsThis unknown targets ARID1A/BAF250
View all literature mentionsThis unknown targets PBRM1
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets SMARCC2
View all literature mentionsThis monoclonal targets V5-Probe (G-14)
View all literature mentionsThis polyclonal targets BRG1 - ChIP Grade
View all literature mentionsThis monoclonal targets BRG1 antibody [EPNCIR111A]
View all literature mentionsThis unknown targets SS18/SSX1 fusion
View all literature mentionsThis polyclonal targets HA EPITOPE TAG Antibody
View all literature mentionsThis monoclonal targets DPF2
View all literature mentionsThis polyclonal targets RNA polymerase II CTD repeat YSPTSPS (phospho S5) antibody - ChIP Grade
View all literature mentionsThis polyclonal targets SMARCC1
View all literature mentionsThis unknown targets Goat Mouse IgG (H L)-HRP Conjugate
View all literature mentionsThis unknown targets SMARCB1/SNF5
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentions