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    In vivo binding of NF-κB to the IκBβ promoter is insufficient for transcriptional activation


    Griffin, Bryan D. and Moynagh, Paul N. (2006) In vivo binding of NF-κB to the IκBβ promoter is insufficient for transcriptional activation. Biochemical Journal, 400. pp. 115-125. ISSN 0264-6021

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    Abstract

    Despite certain structural and biochemical similarities, differences exist in the function of the NF-κB (nuclear factor κB) inhibitory proteins IκBα (inhibitory κBα) and IκBβ. The functional disparity arises in part from variance at the level of gene regulation, and in particular from the substantial induction of IκBα, but not IκBβ, gene expression post-NF-κB activation. In the present study, we probe the differential effects of IL (interleukin)-1β on induction of IκBα and perform the first characterization of the human IκBβ promoter. A consensus NF-κB-binding site, capable of binding NF-κB both in vitro and in vivo, is found in the IκBβ gene 5′ flanking region. However, the IκBβ promoter was not substantially activated by pro-inflammatory cytokines, such as IL-1β and tumour necrosis factor α, that are known to cause strong activation of NF-κB. Furthermore, in contrast with IκBα, NF-κB activation did not increase expression of endogenous IκBβ as assessed by analysis of mRNA and protein levels. Unlike κB-responsive promoters, IκBβ promoter-bound p65 inefficiently recruits RNA polymerase II, which stalls at the promoter. We present evidence that this stalling is likely due to the absence of transcription factor IIH engagement, a prerequisite for RNA polymerase II phosphorylation and transcriptional initiation. Differences in the conformation of promoter-bound NF-κB may underlie the variation in the ability to engage the basal transcriptional apparatus at the IκBβ and κB-responsive promoters. This accounts for the differential expression of IκB family members in response to NF-κB activation and furthers our understanding of the mechanisms involved in transcription factor activity and IκBβ gene regulation. Keywords: chromatin immunoprecipitation (ChIP), cis-element, inhibitory κB (IκB), nuclear factor κB (NF-κB), RNA polymerase II, transcription

    Item Type: Article
    Additional Information: The final version of record is available at http://www.biochemj.org/bj/currentissue.htm
    Keywords: chromatin immunoprecipitation (ChIP); cis-element; inhibitory κB (IκB); nuclear factor κB (NF-κB); RNA polymerase II; transcription;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7190
    Identification Number: https://doi.org/10.1042/BJ20060786
    Depositing User: Professor Paul Moynagh
    Date Deposited: 15 Jul 2016 15:51
    Journal or Publication Title: Biochemical Journal
    Publisher: Portland Press
    Refereed: Yes
    Funders: Health Research Board (HRB), Science Foundation Ireland (SFI)
    URI:

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