The Kinases MSK1 and MSK2 Are Required for Epidermal Growth Factor-induced, but Not Tumor Necrosis Factor-induced, Histone H3 Ser10Phosphorylation

Elizabeth A. Duncan, Vasiliki Anest, Patricia Cogswell, Albert S. Baldwin
2006 Journal of Biological Chemistry  
Phosphorylation of histone H3 protein at serine 10 is an important step in chromatin remodeling during transcriptional transactivation. IB kinase-␣ (IKK-␣) and Mitogen-and Stress-activated protein Kinases 1 and 2 (MSK1/2) have been shown to play key roles in the transcriptional regulation of immediate early genes such as c-fos. Interestingly, IKK-␣ and MSK1/2 have also been implicated as histone H3-Ser 10 kinases. In this work, we have shown that MSK1/2 are required for epidermal growth factor
more » ... rmal growth factor (EGF)-induced, but not tumor necrosis factor-induced, histone H3-Ser 10 phosphorylation, both globally and at specific promoters. Consistent with this, MSK1/2 are required for optimal immediate early c-fos transcription in response to EGF potentially through control of both H3-Ser 10 and promoter-associated cAMP-response element-binding protein phosphorylation. Furthermore, MSK1/2 control EGFinduced IB␣ promoter H3-Ser 10 phosphorylation in the absence of elevated transcription. These studies demonstrate the existence of pathway-specific mechanisms to control histone H3-Ser 10 phosphorylation and gene expression.
doi:10.1074/jbc.m513333200 pmid:16517600 fatcat:cpghxsvtofavxc5ajkasoxx3ni