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Title: Mutant p53 cooperates with ETS2 to promote etoposide resistance [ChIP-Seq]      
dateReleased:
05-02-2012
description:
Mutant p53 (mtp53) promotes chemotherapy resistance through multiple mechanisms including disabling pro-apoptotic proteins and by regulating gene expression. Analysis of promoter regions identified through CHIP-on-CHIP and CHIP-SEQ platforms reveal that the ETS motif (EBS) is prevalent within predicted mtp53 binding sites. We demonstrate that mtp53 regulates gene expression through EBS in promoters, and that ETS2 mediates the interaction with this motif. Importantly, we identified TDP2, a 5’-tyrosyl DNA phosphodiesterase involved in the repair of DNA damage caused by etoposide, as a transcriptional target of mtp53. We demonstrate that suppression of TDP2 sensitizes mtp53 expressing cells to etoposide, and that mtp53 and TDP2 are frequently overexpressed in human lung cancer; thus, our analysis identifies a potentially “druggable” component of mtp53’s gain-of-function activity. Comparison of two different transcriptional binding analysis (ChIP-on-ChIP and ChIP-Seq) for the identification of novel mutant p53 binding.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-36749
refinement:
raw
alternateIdentifiers:
36749
keywords:
functional genomics
dateModified:
06-27-2012
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36749/E-GEOD-36749.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36749/E-GEOD-36749.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36749
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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