H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress
- Anna Sawicka1,
- Dominik Hartl1,6,
- Malgorzata Goiser1,2,
- Oliver Pusch3,
- Roman R. Stocsits2,
- Ido M. Tamir4,
- Karl Mechtler2,5 and
- Christian Seiser1
- 1Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria;
- 2Research Institute of Molecular Pathology, 1030 Vienna, Austria;
- 3Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria;
- 4Campus Science Support Facilities GmbH, 1030 Vienna, Austria;
- 5Protein Chemistry Facility, IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria
- Corresponding author: christian.seiser{at}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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.176255.114.
Freely available online through the Genome Research Open Access option.
- Received March 27, 2014.
- Accepted August 14, 2014.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0.
