Whole genome expression data comparison between WT and Cebpg-/- MEFs.
Transcriptomics Dataset
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General Information
AccessionGSE47777
TitleWhole genome expression data comparison between WT and Cebpg-/- MEFs.
DescriptionC/EBP is an important regulator of oncogene-induced senescence (OIS). Here we show that C/EBP, a heterodimeric partner of C/EBP whose biological functions are not well understood, inhibits cellular senescence. Cebpg-/- MEFs proliferated poorly, entered senescence prematurely, and expressed a pro-inflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBP. The senescence-suppressing activity of C/EBP required its ability to heterodimerize with C/EBP. Covalently linked C/EBP homodimers (~) inhibited the proliferation and tumorigenicity of RasV12-transformed NIH3T3 cells, activated SASP gene expression, and recruited the CBP co-activator in a Ras-dependent manner, whereas ~ heterodimers lacked these capabilities and efficiently rescued proliferation of Cebpg-/- MEFs. C/EBP depletion partially restored growth of C/EBP-deficient cells, indicating that the increased levels of C/EBP homodimers in Cebpg-/- MEFs inhibit proliferation. The proliferative functions of C/EBP are not restricted to fibroblasts, as hematopoietic progenitors from Cebpg-/- bone marrow also displayed impaired growth. Furthermore, high CEBPG expression correlated with poorer clinical prognoses in several human cancers, and C/EBP depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBP neutralizes the cytostatic activity of C/EBP through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47777
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Keyword
Dataset Accession

Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset

Dataset Accession
Tool Name
Direction
Geneset

Small molecules which mimic CEBPG KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse CEBPG KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in CEBPG KO
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in CEBPG KO
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in CEBPG KO
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in CEBPG KO
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in CEBPG KO
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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