Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate
Open accessAbstract
Epigenetic Signals: The lipid sphingosine-1-phosphate (S1P) is a signaling molecule that binds to receptors on the cell surface to initiate biochemical changes that control a range of biological processes from growth and survival to immune reactions. Hait et al. (p. 1254 ) report that S1P can also function by direct binding to the nuclear enzymes, histone deacetylases (HDACs) 1 and 2. The enzyme that generates S1P, sphingosine kinase 2 (ShpK2) is present in the nucleus in complexes with HDAC1 and HDAC2. Generation of S1P and its binding to HDACs inhibited deacetylation of histone. Such histone modification is an epigenetic mechanism that controls gene transcription. Thus, generation of S1P in the nucleus appears to be a signaling mechanism by which cells can control gene expression in response to various stimuli.
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S1P and FTY720-P function as inhibitors of histone deacetylases (HDAC).
“Because S1P and FTY720-P have been reported to function as inhibitors of histone deacetylases (HDAC) (34, 35)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [34]
The paper reports that S1P inhibits HDAC activity, including the activity of HDAC1 and HDAC2 (passage [1], section labeled Abstract; page unavailable). Our copy does not report that FTY720-P inhibits HDACs; searches for FTY720-P and fingolimod phosphate found no supporting passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredS1P has been reported to repress HDAC activity.
“S1P has been reported to repress HDAC activity (34)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [34]
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Research works printed but not linked: 21
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- Authors
- Hait, N. C., Allegood, J., Maceyka, M., Strub, G. M., Harikumar, K. B., Singh, S. K., Luo, C., Marmorstein, R., Kordula, T., Milstien, S., & Spiegel, S.
- Affiliations
- Virginia Commonwealth University (US)
- The Wistar Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Spiegel, Sarah
- ORCID
- Venue
- Science
- Published
- 2009-09-04
- Volume
- 325
- Issue
- 5945
- Pages
- 1254-1257
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2850596
- OpenAlex
- W1996605319
- Cited by
- 997
- References
- 0
- Citations by year
- 2026: 37 · 2025: 33 · 2024: 47 · 2023: 47 · 2022: 50 · 2021: 74 · 2020: 68 · 2019: 55 · 2018: 71 · 2017: 69 · 2016: 65 · 2015: 56 · 2014: 65 · 2013: 74 · 2012: 70
- FWCI
- 23.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA061774)
- National Institute of General Medical Sciences (R01GM060293, R37GM043880)
- National Institute of Neurological Disorders and Stroke (F30NS058008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- sphingosine-1-phosphate, histone acetylation, histone deacetylase, HDAC1, HDAC2, sphingosine kinase 2, histone H3, epigenetic regulation, transcriptional regulation, p21, c-fos, repressor complex
- MeSH terms
- Sphingosine Kinase, Acetylation, Cell Nucleus, Histone Deacetylases, Histones, Humans, Lysine, Lysophospholipids, Nucleosomes, Promoter Regions, Genetic, Repressor Proteins, Sphingosine, Tetradecanoylphorbol Acetate, Genes, fos, Phosphotransferases (Alcohol Group Acceptor), Catalytic Domain, RNA Interference, Epigenesis, Genetic, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors
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