Kruppel-like factor 6 is a co-activator of NF-{kappa}B that mediates p65-dependent transcription of selected downstream genes [Immunology]

March 14th, 2014 by Zhang, Y., Lei, C.-Q., Hu, Y.-H., Xia, T., Li, M., Zhong, B., Shu, H.-B.

The transcription factor NF-κB plays a pivotal role in a broad range of physiological and pathological processes, including development, inflammation and immunity. How NF-κB integrates activating signals to expression of specific sets of target genes is of great interest. Here, we identified Kruppel-like factor 6 (KLF6) as a co-activator of NF-κB after TNFα and IL-1β stimulation. Overexpression of KLF6 enhanced TNFα- and IL-1β- induced activation of NF-κB and transcription of a subset of downstream genes, whereas knockdown of KLF6 had opposite effects. KLF6 interacted with p65 in the nucleus and bound to the promoters of target genes. Upon IL-1β stimulation, KLF6 was recruited to promoters of a subset of NF-κB target genes in a p65-dependent manner, which was in turn required for the optimal binding of p65 to the target gene promoters. Our findings thus identified KLF6 as a previously unknown but essential co-activator of NF-κB and provided new insight into the molecular regulation of p65-dependent gene expression.