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

Author:

Sawicka Anna,Hartl Dominik,Goiser Malgorzata,Pusch Oliver,Stocsits Roman R.,Tamir Ido M.,Mechtler Karl,Seiser Christian

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.

Funder

Austrian Science Fund

Publisher

Cold Spring Harbor Laboratory

Subject

Genetics (clinical),Genetics

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