MAP kinase-mediated c-fos regulation relies on a histone acetylation relay switch.
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.
O'Donnell
Amanda
A
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Yang
Shen-Hsi
SH
Sharrocks
Andrew D
AD
D000107:Acetylation; D005786:Gene Expression Regulation; D016762:Genes, fos; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
D025542:Neurofibromin 1; D016760:Proto-Oncogene Proteins c-fos; D050807:ets-Domain Protein Elk-1; D051548:Histone Acetyltransferases; D020928:Mitogen-Activated Protein Kinases