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Metadata

Name
Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics (ChIP-seq.WT.MEFs)
Repository
Gene Expression Omnibus
Identifier
geo.series:GSE132792
Description
NFkB RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (ChIPseq) and functional (RNAseq in knockouts) datasets. We then dissected each gene's regulatory strategy by testing RelA variants in a novel primary-cell genetic complementation assay. All endogenous target genes required that RelA makes DNA-base-specific contacts, and none could be activated by the DNA binding domain alone. However, endogenous target genes differed widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic timecourse data we reveal gene-specific synergy and redundancy of TA1 and TA2. Given that post-translational modifications control TA1 activity and intrinsic affinity for coactivators determines TA2 activity, the differential TA logics suggests context-dependent vs. context-independent control of endogenous RelA-target genes. While some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NFkB RelA core response.
Data or Study Types
Genome binding/occupancy profiling by high throughput sequencing
Source Organization
National Center for Biotechnology Information
Access Conditions
available
Year
2020
Access Hyperlink
http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE132792

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