Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_sgrna]

ABSTRACT: Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_sgrna]

PROVIDER: PRJNA498627 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8113734_1.fastq.gz	Fastqsanger.gz
	SRR8113734_2.fastq.gz	Fastqsanger.gz
	SRR8113735_1.fastq.gz	Fastqsanger.gz
	SRR8113735_2.fastq.gz	Fastqsanger.gz
	SRR8113736_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_sgrna]

Project description:Chordoma is a primary bone cancer with no approved therapy. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling. These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. In other cancer types, transcriptional CDK inhibitors have been observed to downregulate highly expressed, enhancer-associated oncogenic transcription factors (TFs). In chordoma, we find that T is associated with a 1.5-Mb region containing “super-enhancers” and is the most highly expressed super-enhancer-associated TF. Strikingly, transcriptional CDK inhibition leads to preferential and concentration-dependent downregulation of cellular brachyury protein levels in all models tested. Together, these data demonstrate small-molecule targeting of brachyury TF addiction in chordoma, identify a mechanism of T gene regulation that underlies this therapeutic strategy and provide a blueprint for applying systematic genetic and chemical screening approaches to discover vulnerabilities in genomically quiet cancers.

2019-01-20 | GSE121845 | GEO

Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_compound]

2019-01-20 | GSE121843 | GEO

Small-molecule targeting of brachyury transcription factor addiction in chordoma [ChIP-Seq]

2019-01-20 | GSE109791 | GEO

Small-molecule targeting of brachyury transcription factor addiction in chordoma [ATAC-Seq]

2019-01-20 | GSE109785 | GEO

Small-molecule targeting of brachyury transcription factor addiction in chordoma

Project description:Small-molecule targeting of brachyury transcription factor addiction in chordoma

| PRJNA432043 | ENA

Small-molecule targeting of brachyury transcription factor addiction in chordoma

Project description:Small-molecule targeting of brachyury transcription factor addiction in chordoma

| PRJNA498625 | ENA

Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_compound]

Project description:Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_compound]

| PRJNA498620 | ENA

Small-molecule targeting of brachyury transcription factor addiction in chordoma [ATAC-Seq]

Project description:Small-molecule targeting of brachyury transcription factor addiction in chordoma [ATAC-Seq]

| PRJNA432041 | ENA

Small-molecule targeting of brachyury transcription factor addiction in chordoma [ChIP-Seq]

Project description:Small-molecule targeting of brachyury transcription factor addiction in chordoma [ChIP-Seq]

| PRJNA432044 | ENA

Brachyury ChIP sequencing of human chordoma UCH-1 cell line

Project description:ChIP sequencing of chordoma UCH-1 cell line. A well characterised chordoma cell line which bears all the morphological and immunohistochemical features of a chordoma (large vacuolated slow-growing cells, brachyury and cytokeratin-positive) have been used in this study. Chromatin immunoprecipitation using a well characterised anti-Brachyury antibody which has been used in immunohistochemistry of chordoma samples and previous ChIP studies in other systems. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

2011-10-17 | E-ERAD-23 | biostudies-arrayexpress

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