Chromatin kinases act on transcription factors and histone tails in regulation of inducible transcription
Open accessAbstract
The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide. Using pharmacological and genetic approaches, we identified mitogen- and stress-activated protein kinases (MSKs) as primary mediators of H3S28ph in macrophages. Cell-free transcription assays demonstrated that H3S28ph directly promotes p300/CBP-dependent transcription. Further, MSKs can activate both signal-responsive transcription factors and the chromatin template with additive effects on transcription. Specific inhibition of MSKs in macrophages selectively reduced transcription of stimulation-induced genes. Our results suggest that MSKs incorporate upstream signaling inputs and control multiple downstream regulators of inducible transcription.
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H3S28P is associated with open chromatin and activation of transcription.
“H3S28P, which is associated with open chromatin and activation of transcription (65)”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [65]
The Results section on lineage-specific and stimulation-responsive chromatin reports that H3S28ph correlates with LPS-induced transcription. The Discussion suggests it may make chromatin more permissive, but treats increased chromatin-fiber accessibility as a possibility rather than establishing an association with open chromatin. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredH3S28P may evict SOX9 from nucleosomes following chromatin opening and activation.
“This suggests that H3S28P, which is associated with open chromatin and activation of transcription (65), may evict SOX9 from nucleosomes following chromatin opening and activation.”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [65]
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“This suggests that H3S28P, which is associated with open chromatin and activation of transcription (65), may evict SOX9 from nucleosomes following chromatin opening and activation.”
Background
- Authors
- Josefowicz, S. Z., Shimada, M., Armache, A., Li, C. H., Miller, R. M., Lin, S., Yang, A., Dill, B. D., Molina, H., Park, H.-S., Garcia, B. A., Taunton, J., Roeder, R. G., & Allis, C. D.
- Affiliations
- Rockefeller University (US)
- University of California, San Francisco (US)
- University of Pennsylvania (US)
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Josefowicz, Steven Z.
- Roeder, Robert G.
- Allis, C. David
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 64
- Issue
- 2
- Pages
- 347-361
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5081221
- OpenAlex
- W2539174840
- Cited by
- 84
- References
- 41
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 9 · 2017: 10
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institutes of Health
- National Cancer Institute (R01CA129325)
- National Institute of General Medical Sciences (K99GM113019, R01GM110174, R01GM040922)
- National Institute of Allergy and Infectious Diseases (R01AI118891)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071900)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- histone phosphorylation, macrophages, lipopolysaccharide, transcription factors, inflammatory signaling, histone modifications, transcriptional regulation
- MeSH terms
- Red Fluorescent Protein, Bacterial Proteins, Chromatin, Epithelial Cells, HeLa Cells, Histones, Humans, Kinetics, Luminescent Proteins, Mitosis, Recombinant Fusion Proteins, Time Factors, Transcription Factors, Transcription, Genetic, Models, Statistical, Cell Cycle Proteins, Feedback, Physiological, Cell Line, Tumor, Molecular Imaging
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