Teamwork of clustered low-affinity κB sites and accessory factors regulates transcriptional strength of NF-κB RelA dimers.

ABSTRACT: Non-consensus binding sites of transcription factors (TFs) are often observed within the regulatory elements of genes; however, their effect on transcriptional strength is unclear. Within the promoters and enhancers of NF-κB-responsive genes, we identified clusters of non-consensus κB DNA sites, many exhibiting low affinity for NF-κB in vitro. Deletion of these sites demonstrated their collective critical role in transcription. We explored how these "weak" κB sites exert their influence, especially given the typically low nuclear concentrations of NF-κB. Using proteomics approaches, we identified additional nuclear factors, including other DNA-binding TFs, that could interact with κB site-bound NF-κB RelA. ChIP-seq and RNA-seq analyses suggest that these accessory TFs, referred to as the T

SUBMITTER: Shahabi S 

PROVIDER: S-EPMC12507517 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature