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Title: Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression [Agilent]      
dateReleased:
12-31-2013
description:
Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. High density microarray analysis revealed that G1 release primes and cooperates with the cytokine-driven gene response. This effect is transmitted through CDK6 which shares the ability to regulate expression of inflammatory genes with its functional homologue CDK4. CDK6 contributes to the regulation of inflammatory gene expression by physical and functional cooperation with the NF-κB subunit p65 in the nucleus. ChIPSeq experiments showed a tight co-recruitment of CDK6 and p65 to enhancers and promoters of many transcriptionally active NF-κB target genes. While CDK6 recruitment to distinct chromatin regions of inflammatory target genes had no effect on histone modifications, it was essential for proper loading of NF-κB p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-κB to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer. Four sets of experiments were performed in total (Exp1-4). Within each of these sets biological duplicates (Rep1-2) were included and analyzed. HeLa control cells or cells with established shRNA-mediated knockdown of CDK4 or CDK6 were analyzed. Cells were subjected to cell cycle arrest or were released from the arrested state for 6h. Cells were treated for 30 minutes with Interleukin-1-alpha at the arrested state or after release or were left untreated.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-52465
refinement:
raw
alternateIdentifiers:
52465
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AGIL-28
name:
Agilent Whole Human Genome Microarray 4x44K 014850 G4112F (85 cols x 532 rows)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-52465/E-GEOD-52465.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-52465/E-GEOD-52465.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=GSE52465
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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