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Genome Res. 2014 Nov;24(11):1808-20. doi: 10.1101/gr.176255.114. Epub 2014 Aug 18.

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

Author information

1
Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria;
2
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;
3
Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria;
4
Research Institute of Molecular Pathology, 1030 Vienna, Austria;
5
Campus Science Support Facilities GmbH, 1030 Vienna, Austria;
6
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.
7
Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria; christian.seiser@univie.ac.at.

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.

PMID:
25135956
PMCID:
PMC4216922
DOI:
10.1101/gr.176255.114
[Indexed for MEDLINE]
Free PMC Article

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