Abstract
SummaryGene 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.
Highlights
The modification and remodeling of chromatin structure plays a pivotal role in the control of eukaryotic gene regulation
MAP Kinase Signaling Induces Recruitment of NFI to the c-fos Promoter The c-fos promoter contains a positioned nucleosome located between the Elk-1 binding site within the serum response element (SRE) and the promoter (Figure 1A; Herrera et al, 1997)
We first used chromatin immunoprecipitation (ChIP) assays to ask whether binding of NFI could be detected at the c-fos
Summary
The modification and remodeling of chromatin structure plays a pivotal role in the control of eukaryotic gene regulation (reviewed in Berger, 2002; Workman, 2006). Numerous histone modifications have been identified; one of which, acetylation, has been correlatively linked with gene activation. The molecular mechanisms through which enhanced histone acetylation levels cause target gene activation are largely unknown. Studies have focused on the role of acetylation in promoting the recruitment of additional regulatory proteins to chromatin through direct recognition of the acetylated lysine residues through motifs such as bromodomains (reviewed in Marmorstein and Berger, 2001). Other studies have demonstrated enhanced recruitment and activation of the basal machinery as a consequence of increased histone acetylation levels (Guermah et al, 2006). At the majority of promoters, it is still not clear whether histone acetylation plays additional roles in the transcriptional activation process
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