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Series GSE21761 Query DataSets for GSE21761
Status Public on Aug 09, 2010
Title A large intergenic non-coding RNA induced by p53 mediates global gene repression in the p53 transcriptional response
Organism Mus musculus
Experiment type Expression profiling by array
Summary Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes.
 
Overall design Gene expression profiles of different p53 inducible mouse embryonic fibroblasts (p53LSL/LSL MEFs) across different time points after DNA damage.
A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 transcriptional response.

[1] MEF profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration or adenoGFP as control for 24h and treated with 500nM doxorubicin for the indicated times.
[2] hnRNPKKD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h.
[3] lincP21KD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h.
[4] RAS profiling: For p53 restoration, cultured tumor cell lines were incubated with 500nM 4-hydroxytamoxifen for the indicated times.
 
Contributor(s) Huarte M, Rinn JL
Citation(s) 20673990
Submission date May 10, 2010
Last update date Feb 11, 2019
Contact name Mitchell Guttman
E-mail mguttman@mit.edu
Organization name Broad Institute
Street address 7 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (43)
GSM542409 GFP0hrs [MEF profiling]
GSM542410 GFP1hrs [MEF profiling]
GSM542411 GFP3hrs [MEF profiling]
Relations
BioProject PRJNA127275

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
GSE21761_RAW.tar 161.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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