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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Acetylation
  • Animals
  • Chromatin Immunoprecipitation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Gene Ontology
  • Genome-Wide Association Study
  • HeLa Cells
  • High-Throughput Nucleotide Sequencing
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • MAP Kinase Signaling System / genetics
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Promoter Regions, Genetic / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Serine / metabolism*
  • Stress, Physiological / genetics*
  • Transcriptional Activation*


  • Histones
  • Serine
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • Histone Deacetylases

Associated data

  • GEO/GSE55784