title: H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria;
authors.forename: Anna
authors.initials: A
authors.lastname: Sawicka
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria;
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria; Research Institute of Molecular Pathology, 1030 Vienna, Austria;
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Goiser
authors.affiliation: Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Oliver
authors.initials: O
authors.lastname: Pusch
authors.affiliation: Research Institute of Molecular Pathology, 1030 Vienna, Austria;
authors.forename: Roman R
authors.initials: RR
authors.lastname: Stocsits
authors.affiliation: Campus Science Support Facilities GmbH, 1030 Vienna, Austria;
authors.forename: Ido M
authors.initials: IM
authors.lastname: Tamir
authors.affiliation: Research Institute of Molecular Pathology, 1030 Vienna, Austria; Protein Chemistry Facility, IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria; christian.seiser@univie.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Seiser
mesh_terms: D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D063990:Gene Ontology; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D012694:Serine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D006655:Histone Deacetylases