Abstract
CD1d is a MHC class-like molecule that presents glycolipids to natural killer T (NKT) cells, then regulates innate and adaptive immunity. The regulation of CD1d gene expression in solid tumors is still largely unknown. Gene expression can be epigenetically regulated by DNA methylation and histone acetylation. We found that histone deacetylase inhibitors, trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), induced CD1d gene expression in human (A549 and NCI-H292) and mouse (TC-1 and B16/F0) cancer cells. Simultaneous knockdown of HDAC1 and 2 induced CD1d gene expression. Sp1 inhibitor mitramycin A (MTM) blocked TSA- and SAHA-induced CD1d mRNA expression and Sp1 luciferase activity. Co-transfection of GAL4-Sp1 and Fc-luciferase reporters demonstrated that TSA and SAHA induced Sp1 luciferase reporter activity by enhancing Sp1 transactivation activity. The binding of Sp1 to CD1d promoter and histone H3 acetylation on Sp1 sites were increased by TSA and SAHA. These results indicate that TSA and SAHA could up-regulate CD1d expression in tumor cells through inhibition of HDAC1/2 and activation of Sp1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Antigens, CD1d / genetics
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Antigens, CD1d / metabolism*
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Base Sequence
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Binding Sites
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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Enzyme Activation
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Genes, Reporter
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Histone Deacetylase 1 / genetics
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Histone Deacetylase 1 / metabolism*
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Histone Deacetylase 2 / genetics
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Histone Deacetylase 2 / metabolism
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Histone Deacetylase Inhibitors / pharmacology*
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Histones / genetics
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Histones / metabolism
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Humans
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Hydroxamic Acids / pharmacology
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Luciferases / genetics
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Luciferases / metabolism
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Mice
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Molecular Sequence Data
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Plicamycin / pharmacology
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Promoter Regions, Genetic
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Sp1 Transcription Factor / genetics
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Sp1 Transcription Factor / metabolism*
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Transcriptional Activation
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Transfection
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Vorinostat
Substances
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Antigens, CD1d
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CD1D protein, human
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Cd1d1 protein, mouse
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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RNA, Messenger
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RNA, Small Interfering
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Sp1 Transcription Factor
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trichostatin A
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Vorinostat
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Luciferases
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HDAC1 protein, human
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HDAC2 protein, human
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Hdac1 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylase 2
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Plicamycin