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Series GSE106914

Query DataSets for GSE106914

Status

Public on Jul 30, 2018

Title

Epigenome editing of microsatellite repeat enhancers reveals specific regulatory functions and tumor dependencies [ChIP-Seq]

Organism

Experiment type

Genome binding/occupancy profiling by high throughput sequencing

Summary

Various types of repetitive sequences are dysregulated in cancer but their contributions to oncogenesis are yet to be determined. Here we combine nascent transcription profiling with epigenome editing to test the function of GGAA microsatellites in Ewing sarcoma, a pediatric bone cancer where the oncogenic fusion protein EWS-FLI1 induces chromatin features of active enhancers at this class of repeats. Silencing of chromatin through epigenome editing at specific GGAA repeats abolished local nascent transcription, decreased the expression of neighboring target genes and, in the case of a repeat associated with the SOX2 locus, reduced the growth of tumor xenografts. Our studies directly demonstrate that repeat elements can acquire enhancer functions in cancer and become critical components of oncogenic gene regulation programs.

Raw data for MSC Samples GSM2857574-GSM2857587 are subject to privacy restrictions and were not submitted.

Overall design

ChIP-seq for the histone modifications H3K4me1, H3K4me3, H3K9ac, H3K27ac, H3K27me3 and the transcription factor EWS-FLI1 in mesenchymal stem cells (MSC). EWS-FLI1 was expressed in MSCs with lentiviral expression vectors. ChIP-seq for the histone modifications H3K27ac, H3K9me3 and the transcription factor EWS-FLI1 in Ewing sarcoma cells (A673). dCas9-KRAB and specific guide RNAs targeting a GGAA repeat enhancer either near NKX2-2 or SOX2 were expressed in Ewing sarcoma cells (A673) using a lentiviral expression vector. ChIP-seq for the histone modifications H3K4me3 and H3K27ac in the lung carcinoma cells NCI-H810.

Contributor(s)

Boulay G, Volorio A, Rivera M

Citation(s)

Submission date

Nov 15, 2017

Last update date

May 31, 2019

Contact name

Sowmya Iyer

E-mail(s)

[email protected]

Organization name

Massachusetts General Hospital

Department

Pathology

Street address

149 13th St

City

Boston

State/province

MA

ZIP/Postal code

02129

Country

USA

Platforms (2)

GPL18573	Illumina NextSeq 500 (Homo sapiens)
GPL24268	Illumina Nextseq 500 (Homo sapiens)

Samples (35)

More...

GSM2857574	H3K4me1 ChIP-seq in MSC
GSM2857575	H3K4me3 ChIP-seq in MSC
GSM2857576	H3K9ac ChIP-seq in MSC

GSM2857577	H3K27ac ChIP-seq in MSC
GSM2857578	H3K27me3 ChIP-seq in MSC
GSM2857579	FLI1 ChIP-seq in MSC
GSM2857580	INPUT library in MSC infected with control
GSM2857581	H3K4me1 ChIP-seq in MSC infected with EWSFLI1
GSM2857582	H3K4me3 ChIP-seq in MSC infected with EWSFLI1
GSM2857583	H3K9ac ChIP-seq in MSC infected with EWSFLI1
GSM2857584	H3K27ac ChIP-seq in MSC infected with EWSFLI1
GSM2857585	H3K27me3 ChIP-seq in MSC infected with EWSFLI1
GSM2857586	FLI1 ChIP-seq in MSC infected with EWSFLI1
GSM2857587	INPUT library in MSC infected with EWSFLI1
GSM2857588	FLI1 ChIP-seq in A673.1 cells with dCAS9 targeting control
GSM2857589	FLI1 ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 1)
GSM2857590	FLI1 ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 2)
GSM2857591	H3K9me3 ChIP-seq in A673.1 cells with dCAS9 targeting control
GSM2857592	H3K9me3 ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 1)
GSM2857593	H3K9me3 ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 2)
GSM2857594	H3K27ac ChIP-seq in A673.1 cells with dCAS9 targeting control
GSM2857595	H3K27ac ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 1)
GSM2857596	H3K27ac ChIP-seq in A673.1 cells with dCAS9 targeting enhancer of NKX2-2 (gRNA 2)
GSM2857597	FLI1 ChIP-seq in A673.2 cells with dCAS9 targeting control
GSM2857598	FLI1 ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 1)
GSM2857599	FLI1 ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 2)
GSM2857600	H3K9me3 ChIP-seq in A673.2 cells with dCAS9 targeting control
GSM2857601	H3K9me3 ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 1)
GSM2857602	H3K9me3 ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 2)
GSM2857603	H3K27ac ChIP-seq in A673.2 cells with dCAS9 targeting control
GSM2857604	H3K27ac ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 1)
GSM2857605	H3K27ac ChIP-seq in A673.2 cells with dCAS9 targeting enhancer of SOX2 (gRNA 2)
GSM2857606	H3K4me3 ChIP-seq in NCIH810 cells
GSM2857607	H3K27ac ChIP-seq in NCIH810 cells
GSM2857608	INPUT library in NCIH810 cells

This SubSeries is part of SuperSeries:

Epigenome editing of microsatellite repeat enhancers reveals specific regulatory functions and tumor dependencies

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
GSE106914_RAW.tar	7.2 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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