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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 Homo sapiens
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) 30042132
Submission date Nov 15, 2017
Last update date May 31, 2019
Contact name Sowmya Iyer
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)
GSM2857574 H3K4me1 ChIP-seq in MSC
GSM2857575 H3K4me3 ChIP-seq in MSC
GSM2857576 H3K9ac ChIP-seq in MSC
This SubSeries is part of SuperSeries:
GSE106925 Epigenome editing of microsatellite repeat enhancers reveals specific regulatory functions and tumor dependencies
BioProject PRJNA418456
SRA SRP125032

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Supplementary file Size Download File type/resource
GSE106914_RAW.tar 7.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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