github link
Accession IconSRP050446

Signaling to histone H3 for augmented transcription in the inflammatory response

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge IconIllumina HiSeq 2000

Submitter Supplied Information

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 cell’s 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. Overall design: Primary mouse bone marrow derived macrophages (BMDM) were used for NGS experiments. Briefly, BMDM were used unstimulated or following stimulation with S. typhosa LPS (100ng/mL) for the indicated period of time. Included in this submission are RNA-seq data for control DMSO treated BMDM (60'' and 120'' LPS stimulation), RMM-64 (5 uM) treated (60’ and 120’), SB747651A (5 uM) treated (60’ and 120’), and C646 (37.5 uM) teated (60’ and 120’). Further, ChIP-seq data for H3S28p time-course in BMDM stimulated with LPS includes one file each for 0’, 30’, 60’, 120’, 180’, 240’, and one file each at 0’ and 30’ for control DMSO treated, RMM-64 treated, SB747651A treated, and C646 treated BMDM. Also provided is an H3K27ac ChIP-seq time course in LPS stimulated BMDM: 0’, 30’, 120’, 180’, 240’.
PubMed ID
Total Samples
12
Submitter’s Institution
No associated institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Processing Information
Additional Metadata
No rows found
Loading...