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Teamwork of clustered low-affinity κB sites and accessory factors regulates transcriptional strength of NF-κB RelA dimers [ChIP-seq]

ABSTRACT: Non-consensus binding sites of transcription factors are often observed within the promoters and enhancers of various 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 concentration 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 without binding to DNA directly. ChIP-seq and RNA-seq analyses suggest that these accessory TFs, referred to as the cofactors of NF-κB, facilitate dynamic recruitment of NF-κB to the clustered κB sites. Overall, the occupancy of NF-κB at promoters and enhancers appears to be defined by a collective contribution from all κB sites, both weak and strong, in association with specific cofactors. This congregation of multiple factors within dynamic transcriptional complexes is likely a common feature of transcriptional programs.

ORGANISM(S): Mus musculus

PROVIDER: GSE287359 | GEO | 2025/01/22

REPOSITORIES: GEO

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Teamwork of clustered low-affinity κB sites and accessory factors regulates transcriptional strength of NF-κB RelA dimers [RNA-seq]

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