Journal
GENOME RESEARCH
Volume 24, Issue 11, Pages 1808-1820Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.176255.114
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Funding
- Austrian Science Fund (FWF) [P22340, P25807, W1220]
- GEN-AU project Epigenetic Regulation of Cell Fate Decisions (Federal Ministry for Education, Science, and Culture)
- Austrian Science Fund (FWF) [P 25807] Funding Source: researchfish
- Austrian Science Fund (FWF) [P25807] Funding Source: Austrian Science Fund (FWF)
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The selectivity of transcriptional responses to extracellular cues is reflected by the deposition of stimulus-specific chromatin marks. Although histone H3 phosphorylation is a target of numerous signaling pathways, its role in transcriptional regulation remains poorly understood. Here, for the first time, we report a genome-wide analysis of H3S28 phosphorylation in a mammalian system in the context of stress signaling. We found that this mark targets as many as 50% of all stress-induced genes, underlining its importance in signal-induced transcription. By combining ChIP-seq, RNA-seq, and mass spectrometry we identified the factors involved in the biological interpretation of this histone modification. We found that MSK1/2-mediated phosphorylation of H3S28 at stress-responsive promoters contributes to the dissociation of HDAC corepressor complexes and thereby to enhanced local histone acetylation and subsequent transcriptional activation of stress-induced genes. Our data reveal a novel function of the H3S28ph mark in the activation of mammalian genes in response to MAP kinase pathway activation.
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