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Series GSE94275

Query DataSets for GSE94275

Status

Public on Aug 24, 2017

Title

Cancer-specific retargeting of BAF complexes by a prion-like domain [ChIP-Seq]

Organism

Experiment type

Genome binding/occupancy profiling by high throughput sequencing

Summary

Alterations in the function of transcriptional regulators can orchestrate oncogenic programs that are critical for the transformation and survival of cancer cells. Here we show that the BAF chromatin remodeling complex, which is mutated in over 20% of human tumors, interacts with EWSR1, a member of the FET family of proteins containing prion-like domains that are frequent partners in oncogenic fusions with transcription factors. In Ewing sarcoma, characterized by the EWS-FLI1 fusion, we find that the BAF complex is recruited by EWS-FLI1 to tumor specific enhancers at GGAA microsatellite repeats and contributes to the activation of target genes. This process depends on tyrosine residues that are necessary for the aggregation properties of the EWSR1 prion-like domain and is a neomorphic feature of EWS-FLI1 compared to the wild type ETS transcription factor FLI1. Furthermore, fusion of short fragments of the EWSR1 prion-like domain to FLI1 is sufficient to recapitulate EWS-FLI1-mediated gene expression. Our studies demonstrate that the aggregation properties of prion-like domains can retarget chromatin regulatory complexes to establish and maintain oncogenic gene expression and proliferation.

Overall design

ChIP-seq for the BAF complex subunits BAF155 and SMARCA2 in Ewing sarcoma cells (SK-N-MC). EWS-FLI1 was knocked-down with lentiviral shRNA. HA-tagged EWSR1 was expressed in Ewing sarcoma cells (A673) using a lentiviral expression vector and ChIP-seq was performed using an anti-HA antibody.
ChIP-seq for the histone modification H3K27ac, the transcription factor FLI1 and the BAF subunit BAF155 in mesenchymal stem cells (MSC). EWS-FLI1, wild-type FLI1 and the mutant proteins EWS(YS37)-FLI1, SYGQ2-FLI1 and BAF47-FLI1 were expressed in MSCs with lentiviral expression vectors. The FLI1 antibody used recognizes FLI1, EWS-FLI1 and the mutant proteins.

Raw data not provided for primary cells due to patient privacy concerns. Submitter states that the raw data for these samples will be submitted to dbGaP.

Contributor(s)

Boulay G, Rivera M

Citation(s)

Submission date

Jan 30, 2017

Last update date

May 15, 2019

Contact name

Sowmya Iyer

E-mail(s)

sowmya.iyer@mgh.harvard.edu

Organization name

Massachusetts General Hospital

Department

Pathology

Street address

149 13th St

City

Boston

State/province

MA

ZIP/Postal code

02129

Country

USA

Platforms (1)

Illumina NextSeq 500 (Homo sapiens)

Samples (43)

More...

GSM2472081	HA ChIP-seq in A673 cell line infected with GFP
GSM2472082	HA ChIP-seq in A673 cell line infected with HA-EWSR1
GSM2472083	BAF155 ChIP-seq in MSC1 infected with control

GSM2472084	FLI1 ChIP-seq in MSC1 infected with control
GSM2472085	H3K27ac ChIP-seq in MSC1 infected with control
GSM2472086	INPUT library in MSC1 infected with control
GSM2472087	BAF155 ChIP-seq in MSC1 infected with EWSFLI1
GSM2472088	FLI1 ChIP-seq in MSC1 infected with EWSFLI1
GSM2472089	H3K27ac ChIP-seq in MSC1 infected with EWSFLI1
GSM2472090	INPUT library in MSC1 infected with EWSFLI1
GSM2472091	BAF155 ChIP-seq in MSC1 infected with wild-type FLI1
GSM2472092	FLI1 ChIP-seq in MSC1 infected with wild-type FLI1
GSM2472093	H3K27ac ChIP-seq in MSC1 infected with wild-type FLI1
GSM2472094	INPUT library in MSC1 infected with wild-type FLI1
GSM2472095	BAF155 ChIP-seq in MSC2 infected with control
GSM2472096	FLI1 ChIP-seq in MSC2 infected with control
GSM2472097	H3K27ac ChIP-seq in MSC2 infected with control
GSM2472098	BAF155 ChIP-seq in MSC2 infected with EWS(YS37)-FLI1
GSM2472099	FLI1 ChIP-seq in MSC2 infected with EWS(YS37)-FLI1
GSM2472100	H3K27ac ChIP-seq in MSC2 infected with EWS(YS37)-FLI1
GSM2472101	BAF155 ChIP-seq in MSC2 infected with EWSFLI1
GSM2472102	FLI1 ChIP-seq in MSC2 infected with EWSFLI1
GSM2472103	H3K27ac ChIP-seq in MSC2 infected with EWSFLI1
GSM2472104	BAF155 ChIP-seq in MSC3 infected with control
GSM2472105	FLI1 ChIP-seq in MSC3 infected with control
GSM2472106	H3K27ac ChIP-seq in MSC3 infected with control
GSM2472107	BAF155 ChIP-seq in MSC3 infected with EWSFLI1
GSM2472108	FLI1 ChIP-seq in MSC3 infected with EWSFLI1
GSM2472109	H3K27ac ChIP-seq in MSC3 infected with EWSFLI1
GSM2472110	BAF155 ChIP-seq in MSC3 infected with SYGQ2-FLI1
GSM2472111	FLI1 ChIP-seq in MSC3 infected with SYGQ2-FLI1
GSM2472112	H3K27ac ChIP-seq in MSC3 infected with SYGQ2-FLI1
GSM2472113	FLI1 ChIP-seq in MSC4 infected with BAF47FLI1
GSM2472114	H3K27ac ChIP-seq in MSC4 infected with BAF47FLI1
GSM2472115	INPUT library in MSC4 infected with BAF47FLI1
GSM2472116	FLI1 ChIP-seq in MSC4 infected with control
GSM2472117	H3K27ac ChIP-seq in MSC4 infected with control
GSM2472118	INPUT library in MSC4 infected with control
GSM2472119	SMARCA2 ChIP-seq in SKNMC cell line infected with shEWSFLI1
GSM2472120	SMARCA2 ChIP-seq in SKNMC cell line infected with shGFP
GSM2472121	BAF155 ChIP-seq in SKNMC cell line
GSM2472122	BAF155 ChIP-seq in SKNMC cell line infected with shEWSFLI1
GSM2472123	BAF155 ChIP-seq in SKNMC cell line infected with shGFP

This SubSeries is part of SuperSeries:

Cancer-specific retargeting of BAF complexes by a prion-like domain

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE94275_RAW.tar	10.2 Gb	(http)(custom)	TAR (of BW)
SRA Run Selector
Raw data are available in SRA
Processed data provided as supplementary file

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