MAP Kinase-Mediated c-fos Regulation Relies on a Histone Acetylation Relay Switch

Amanda O'Donnell, Shen Hsi Yang, Andrew D. Sharrocks

    Research output: Contribution to journalArticlepeer-review


    Gene activation is often associated with high levels of histone acetylation. Enhanced acetylation levels can promote the recruitment of further chromatin modifying complexes or the basal transcription machinery. Here, we have studied MAP kinase-mediated upregulation of c-fos and uncover a role for histone acetylation in promoting the recruitment of a second transcription factor, NFI. MAP kinase signaling to Elk-1 enhances the net histone acetylase activity associated with the c-fos promoter, which leads to changes in the acetylation state and structure of a promoter-proximal nucleosome, which allows NFI binding. Binding of NFI provides a permissive state for the recruitment of basal machinery and subsequent promoter activation. Our results provide insights into how MAP kinase signaling promotes inducible gene expression; phosphorylation of recipient transcription factors (primary effectors) triggers a HAT relay switch, which facilitates the recruitment of additional transcription factors (secondary effectors) through alteration of the local nucleosomal structure. © 2008 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)780-785
    Number of pages5
    JournalMolecular Cell
    Issue number6
    Publication statusPublished - 28 Mar 2008


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