GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE82330 Query DataSets for GSE82330
Status Public on Jul 07, 2016
Title INO80 governs super-enhancer-mediated oncogenic transcription and tumor growth in melanoma [ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Super-enhancers (SEs) are large genomic regions with high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared to normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, as well as tumorigenesis and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies more than 90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are specifically expressed in melanomas compared to melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function, and suggest a novel strategy for disrupting SEs in cancer treatment.
Overall design Human melanoma cell line A375 cells were infected with shNT or shIno80, and total RNA was extracted 2, 3, 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, either wild type A375 and SK-MEL-147, or A375 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.
Contributor(s) Zhou B, Wang L, Bennett B, Cox AD, Hu G
Citation(s) 27340176
Submission date Jun 07, 2016
Last update date May 15, 2019
Contact name Li Wang
Organization name NIH
Street address 111 T.W. Alexander Dr
City Durham
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (2)
GSM2190573 A375_shNT_ATAC
GSM2190574 A375_shIno80_ATAC
This SubSeries is part of SuperSeries:
GSE82334 INO80 governs super-enhancer-mediated oncogenic transcription and tumor growth in melanoma
BioProject PRJNA328059
SRA SRP096038

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE82330_RAW.tar 208.0 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap