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  • Growth factor-induced activation of MSK2 leads to phosphorylation of H3K9me2S10 and corresponding changes in gene expression.

Growth factor-induced activation of MSK2 leads to phosphorylation of H3K9me2S10 and corresponding changes in gene expression.

Science advances (2024-03-13)
Karen G Wong, Yu-Chia F Cheng, Vincent H Wu, Anna A Kiseleva, Jun Li, Andrey Poleshko, Cheryl L Smith, Jonathan A Epstein
ABSTRACT

Extracellular signals are transmitted through kinase cascades to modulate gene expression, but it remains unclear how epigenetic changes regulate this response. Here, we provide evidence that growth factor-stimulated changes in the transcript levels of many responsive genes are accompanied by increases in histone phosphorylation levels, specifically at histone H3 serine-10 when the adjacent lysine-9 is dimethylated (H3K9me2S10). Imaging and proteomic approaches show that epidermal growth factor (EGF) stimulation results in H3K9me2S10 phosphorylation, which occurs in genomic regions enriched for regulatory enhancers of EGF-responsive genes. We also demonstrate that the EGF-induced increase in H3K9me2S10ph is dependent on the nuclear kinase MSK2, and this subset of EGF-induced genes is dependent on MSK2 for transcription. Together, our work indicates that growth factor-induced changes in chromatin state can mediate the activation of downstream genes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium butyrate, ≥98.5% (GC)
Sigma-Aldrich
PKG Inhibitor, The PKG Inhibitor controls the biological activity of PKG. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.
Sigma-Aldrich
Anti-Histone H3 Antibody (Dimethyl K9, Phospho S10), clone 6HH3-2C5, ascites fluid, clone 6HH3-2C5, from mouse