| First Author | Ngo KA | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 8 | Pages | 2758-2775.e6 |
| PubMed ID | 32101750 | Mgi Jnum | J:288116 |
| Mgi Id | MGI:6415520 | Doi | 10.1016/j.celrep.2020.01.108 |
| Citation | Ngo KA, et al. (2020) Dissecting the Regulatory Strategies of NF-kappaB RelA Target Genes in the Inflammatory Response Reveals Differential Transactivation Logics. Cell Rep 30(8):2758-2775.e6 |
| abstractText | Nuclear factor kappaB (NF-kappaB) RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (chromatin immunoprecipitation sequencing [ChIP-seq]) and functional (RNA sequencing [RNA-seq] in knockouts) datasets. We then dissected each gene's regulatory strategy by testing RelA variants in a primary-cell genetic-complementation assay. All endogenous target genes require RelA to make DNA-base-specific contacts, and none are activatable by the DNA binding domain alone. However, endogenous target genes differ widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic time-course data, we reveal the 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 versus context-independent control of endogenous RelA-target genes. Although some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NF-kappaB RelA core response. |
