NF-κB c-Rel Dictates the Inflammatory Threshold by Acting as a Transcriptional Repressor.

ABSTRACT: NF-κB/Rel family of transcription factors plays a central role in initiation and resolution of inflammatory responses. Here, we identified a function of the NF-κB subunit c-Rel as a transcriptional repressor of inflammatory genes. Genetic deletion of c-Rel substantially potentiates the expression of several TNF-α-induced RelA-dependent mediators of inflammation. v-Rel, the viral homologue of c-Rel, but not RelB, also possesses this repressive function. Mechanistically, we found that c-Rel selectively binds to the co-repressor HDAC1 and competitively binds to the DNA mediating HDAC1 recruitment to the promoters of inflammatory genes. A specific point mutation at tyrosine²⁵ in c-Rel's DNA-binding domain, for which a missense single nucleotide variation (Y25H) exists in humans, com

SUBMITTER: de Jesus TJ 

PROVIDER: S-EPMC7031323 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature