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Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression

ABSTRACT: Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression

PROVIDER: PRJNA229059 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1031960.fastq.gz	Fastqsanger.gz
	SRR1031961.fastq.gz	Fastqsanger.gz
	SRR1031962.fastq.gz	Fastqsanger.gz
	SRR1031953.fastq.gz	Fastqsanger.gz
	SRR1031954.fastq.gz	Fastqsanger.gz

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Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression

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Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression [Agilent]

Project 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.

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