Signaling to histone H3 for augmented transcription in the inflammatory response
Transcriptomics Dataset
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| Accession | GSE63792 |
| Title | Signaling to histone H3 for augmented transcription in the inflammatory response |
| Description | The inflammatory response depends upon selective, rapid transcription initiation and high-level generation of gene products for defense against pathogens and environmental insult1,2. Kinase cascades are broadly employed for rapid transmission of extracellular information, thereby regulating the cells environmental response. These pathways play a prominent role in the inflammatory process. Several kinases directly phosphorylate histone proteins in chromatin, representing a mechanism for the rapid modification of chromatin with the potential to regulate selective transcription responses to environmental cues3-10. However, the molecular functions of specific histone phosphorylation events in transcription are poorly understood. Here, we demonstrate a direct effect of histone H3 phosphorylation at serine 28 (H3S28p) on transcription activation and describe a prominent role for H3S28p in the amplification of inflammatory gene transcription following stimulation of mouse macrophages with bacterial lipopolysaccharide (LPS). We identify MSK kinases as the non-redundant kinases that mediate the rapid, stimulation-dependent deposition of H3S28p on chromatin. Pharmacological approaches, including the use of a novel chemical agent, reveal that MSK inhibition abolishes stimulation-dependent accumulation of H3S28p at LPS-induced genes and reduces production of inflammatory gene products. Mechanistically, H3S28p directly increases transcriptional output by augmenting recruitment of the transcription co-activator and histone acetyltransferase (HAT) p300, and increasing its HAT activity. Our results reveal a delegated role for H3S28p in selective augmentation of transcription during the rapid cellular response to environmental cues. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63792 |
| Repository | Gene Expression Omnibus |
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