H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress

• Published in: Genome research Vol. 24; no. 11; pp. 1808 - 1820
• Main Authors: Sawicka, Anna, Hartl, Dominik, Goiser, Malgorzata, Pusch, Oliver, Stocsits, Roman R., Tamir, Ido M., Mechtler, Karl, Seiser, Christian
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.11.2014
• Subjects: 3T3 Cells; Acetylation; Animals; Chromatin Immunoprecipitation; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression Profiling; Gene Ontology; Genome-Wide Association Study; HeLa Cells; High-Throughput Nucleotide Sequencing; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Histones - metabolism; Humans; MAP Kinase Signaling System - genetics; Mice; Oligonucleotide Array Sequence Analysis; Phosphorylation; Promoter Regions, Genetic - genetics; Ribosomal Protein S6 Kinases, 90-kDa - genetics; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; Serine - metabolism; Stress, Physiological - genetics; Transcriptional Activation
• ISSN: 1088-9051; 1549-5469; 1549-5469
• DOI: 10.1101/gr.176255.114

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.