Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

60 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differentiation of NUT midline carcinoma by epigenomic reprogramming

ABSTRACT: Knockdown of the oncogene, BRD4-NUT, in a rare cancer, termed NUTmidline carcinoma (NMC), results in morphologic features consistent with squamous differentiation. Treatment with the HDAC-inhibitor, TSA, appears to cause the same phenotype. Here, we use gene expression profiling to compare the changes in gene expression following BRD4-NUT knockdown and TSA treatment. RNA was extracted from two BRD4-NUT-expressing NMC cell lines, PER-403 and TC-797, 24h following siRNA knockdown versus control in duplicate. RNA was extracted from two BRD4-NUT-expressing NMC cell lines, PER-403 and TC-797, 24h following treatment with TSA versus etoh control in triplicate

ORGANISM(S): Homo sapiens

SUBMITTER: Chris French

PROVIDER: E-GEOD-18668 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

H3K9/14Ac in TC-797 genome

Project description:The goal is to localize "active" histone marks known to bind BRD4-NUT in the NMC genome. Characterization of the reference epigenome in humans by use of ChIP-Seq in the TC-797 human NMC cell line. ChIP-seq of untreated TC-797 cells using H3K9/14Ac antibodies versus IgG control.

2013-03-05 | E-GEOD-36512 | biostudies-arrayexpress

H3K9/14Ac in TC-797 genome

2013-03-05 | GSE36512 | GEO

Differentiation of NUT midline carcinoma by epigenomic reprogramming

Project description:Knockdown of the oncogene, BRD4-NUT, in a rare cancer, termed NUTmidline carcinoma (NMC), results in morphologic features consistent with squamous differentiation. Treatment with the HDAC-inhibitor, TSA, appears to cause the same phenotype. Here, we use gene expression profiling to compare the changes in gene expression following BRD4-NUT knockdown and TSA treatment.

2011-07-01 | GSE18668 | GEO

ChIP-seq analysis of BRD4-NUT and H3K27ac distribution in NUT Carcinoma cell line TC-797 treated with DMSO or Panobinostat

Project description:BRD4-NUT and H3K27ac are depleted from megadomains in NUT Carcinoma (NC) cell line TC-797 after treatment with Panobinostat.

2021-07-14 | GSE179692 | GEO

Recovery and analysis of nascent RNA

Project description:Nascent transcription profiles are shown for scaled megadomains and 100kb flanking regions before BRD4-NUT induction (0h) and at different time points (2h, 3h, 7h) following induction in 293T cells. Increase of the transcription from 0h to 7h after induction. Average level of transcriptional activity is reduced within the megadomains and their flanking regions following JQ1 treatment of TC-797 cells. Profile of nascent RNA-seq is shown for cells without JQ1 treatment, and for cells 1hr, 2.5hr and 4hr following JQ1 treatment. Recovery and analysis of nascent RNA

2015-07-14 | E-GEOD-70871 | biostudies-arrayexpress

Chip-seq mapping of active chromatin marks in BRD4-NUT and different NMC cells

Project description:BRD4-NUT megadomains is an order of magnitude larger than super-enhancer regions and displays a more continuously enriched profile rather than appearing as a cluster of individual peaks. Chip-seq mapping of active chromatin marks in BRD4-NUT and different NMC cells

2015-07-14 | E-GEOD-70870 | biostudies-arrayexpress

Chromatin-associated protein interactions drive megadomain formation in NUT midline carcinoma

Project description:To investigate the mechanism that drives dramatic mistargeting of active chromatin in NUT-midline carcinoma, we have identified protein interactions unique to the BRD4-NUT fusion oncoprotein compared to wild type BRD4. Using crosslinking, affinity purification, and mass spectrometry, we identify the p300 acetyltransferase as ectopically associated with BRD4 through the NUT fusion in both NMC and non-NMC cell types. We also identify ZNF532 among a number of candidates uniquely associated with BRD4-NUT in NMC patient cells but not present in 293T cells. p300 and ZNF532 are both implicated in feed-forward regulatory loops leading to propagation of the oncogenic regulatory complex in BRD4-NUT patient cells. Extending our biochemical findings, we independently identified a novel ZNF532-NUT translocation fusion in a newly diagnosed NMC patient. ChIP-seq of key players: NUT, ZNF532, BRD4, p300, and anti-H3K27ac, reveals the formation of ZNF532-NUT-associated hyperacetylated megadomains, distinctly localized, but otherwise analogous to those found in BRD4-NUT patient cells. Our results support a model in which NMC is caused by a cascade of misregulation that is initiated by ectopic protein-protein interactions on chromatin between NUT and several distinct, but interacting, components of BRD4 regulatory complexes.

2017-08-22 | GSE96775 | GEO

Oncogenic BRD4-NUT protein interactions

Project description:To investigate the mechanism that drives dramatic mistargeting of active chromatin in NUT midline carcinoma, we have identified protein interactions unique to the BRD4-NUT fusion oncoprotein compared to wild type BRD4. Using crosslinking, affinity purification, and mass spectrometry, we identified the EP300 acetyltransferase as uniquely associated with BRD4 through the NUT fusion in both NMC and non-NMC cell types. We also discovered ZNF532 among a small number of candidates associated with BRD4-NUT in NMC patient cells but not present in 293T cells.

2017-04-05 | PXD005786 | Pride

Combined targeting of the BRD4-NUT-p300 axis in NUT midline carcinoma by dual selective bromodomain inhibitor, NEO2734

Project description:NUT midline carcinoma (NMC) is a rare, aggressive subtype of squamous carcinoma that is driven by the BRD4-NUT fusion oncoprotein. BRD4, a BET protein, binds to chromatin through its two bromodomains, and NUT recruits the p300 histone acetyltransferse (HAT) to activate transcription of oncogenic target genes. BET selective bromodomain inhibitors have demonstrated on-target activity in NMC patients, but with limited efficacy. P300, like BRD4, contains a bromodomain. We show that combining selective p300/CBP and BET bromodomain inhibitors, GNE-781 and OTX015, respectively, induces synergistic inhibition of NMC growth. Treatment of NMC cells with the novel dual p300/CBP and BET bromodomain selective inhibitor, NEO2734, potently inhibits growth and induces differentiation of NMC cells in vitro; findings that correspond with potentiated transcriptional effects from combined BET and p300 bromodomain inhibition. In three disseminated NMC xenograft models, NEO2734 provided greater growth inhibition, with tumor regression and significant survival benefit seen in two of three models, compared with a lead clinical BET inhibitor or 'standard' chemotherapy.

2020-06-19 | GSE142481 | GEO

RNA-seq on NUT Carcinoma (NC) cell lines treated with DMSO, Panobinostat or IRBM6

Project description:HDAC inhibitor induce transcriptional program driving cellular differentiation and growth arrest in NUT Carcinoma (NC) cell lines TC-797 and 10-15.

2021-07-14 | GSE179693 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data