DNA element downstream of the κB site in the Lcn2 promoter is required for transcriptional activation by IκBζ and NF‐κB p50. (20th June 2014)

• Record Type: Journal Article
• Authors: Kohda, Akira; Yamazaki, Soh; Sumimoto, Hideki
• Is Part Of: Genes to cells. Volume 19:Number 8(2014:Aug.)
• Page Start: 620
• Page End: 628
• Publication Date: 2014-06-20
• Subjects: Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12162
• Languages: English
• ISSNs: 1356-9597

Abstract

<abstract abstract-type="main" id="gtc12162-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The nuclear protein I<italic>κ</italic>B<italic>ζ</italic> activates transcription of a subset of NF‐<italic>κ</italic>B‐dependent innate immune genes such as <italic>Lcn2</italic> encoding the antibacterial protein lipocalin‐2. I<italic>κ</italic>B<italic>ζ</italic> functions as a coactivator via its interaction with NF‐<italic>κ</italic>B p50, which contains a DNA‐binding Rel‐homology domain but lacks a transcriptional activation domain. However <italic>cis</italic>‐regulatory elements involved in I<italic>κ</italic>B<italic>ζ</italic> function have remained unknown. Here, we show that, although I<italic>κ</italic>B<italic>ζ</italic> by itself is unable to associate with the <italic>Lcn2</italic> promoter, I<italic>κ</italic>B<italic>ζ</italic> interacts with the promoter via p50 binding to the NF‐<italic>κ</italic>B‐binding site (<italic>κ</italic>B site) and the interaction also requires the pyrimidine‐rich site (CCCCTC) that localizes seven bases downstream of the <italic>κ</italic>B site. The pyrimidine‐rich site is also essential for I<italic>κ</italic>B<italic>ζ</italic>‐mediated activation of the <italic>Lcn2</italic> gene. Introduction of both sites into an I<italic>κ</italic>B<italic>ζ</italic>‐independent gene culminates in I<italic>κ</italic>B<italic>ζ</italic>–p50–DNA complex formation and transcriptional activation. Furthermore, spacing between the two sites is crucial for both I<italic>κ</italic>B<italic>ζ</italic>–DNA interaction and I<italic>κ</italic>B<italic>ζ</italic>‐mediated gene activation. Thus, the pyrimidine‐rich I<italic>κ</italic>B<italic>ζ</italic>‐responsive site plays an essential role in productive interaction of I<italic>κ</italic>B<italic>ζ</italic> with the p50–DNA complex.</p> </abstract>