H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress
- Anna Sawicka1,
- Dominik Hartl1,
- Malgorzata Goiser1,
- Oliver Pusch1,
- Roman R Stocsits2,
- Ido Tamir2,
- Karl Mechtler2 and
- Christian Seiser1,3
- ↵* Corresponding author; email: christian.seiser{at}univie.ac.at
Abstract
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 still remains poorly understood. Here we report for the first time a genome-wide analysis of H3S28ph in the 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 spectrometry we identified the factors involved in 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 co-repressor complexes and thereby to enhanced local histone acetylation and subsequent transcriptional activation of stress-induced genes. Our data reveals a novel function of the H3S28ph mark in the activation of mammalian genes in response to MAP kinase pathway activation.
- Received March 27, 2014.
- Accepted August 14, 2014.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.
