Role of histone deacetylase in the expression of CTP:phosphocholine cytidylyltransferase alpha.
Histone acetylation plays an important role in chromatin remodeling and gene expression. The molecular mechanisms involved in cell-specific expression of CTP:phosphocholine cytidylyltransferase alpha (CTalpha) are not fully understood. In this study, we investigated whether or not histone deacetylation is involved in repression of CTalpha expression in quiescent C3H10T1/2 mouse embryo fibroblasts. We have examined the contributions of the Sp1 and E2F binding sites in the repression of CTalpha gene expression. Immunoprecipitation experiments showed that histone deacetylase 1 (HDAC1) and HDAC activity are associated with Sp1 in serum-starved cells or during serum stimulation. However, HDAC1 association with E2F was only detected in serum-starved cells. By chromatin immunoprecipitation assays, we detected both direct and indirect association of HDAC1 with the CTalpha promoter. Treatment with the HDAC inhibitor trichostatin A induced CTalpha expression. Our data suggest that HDAC1 plays a critical role in CTalpha repression and that Sp1 and E2F may serve as key targets for HDAC1-mediated CTalpha repression in fibroblasts.
Banchio
Claudia
C
Department of Biochemistry and Canadian Institutes of Health Research Group in Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. cbanchio@fbioyf.unr.edu.ar
Lingrell
Susanne
S
Vance
Dennis E
DE
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006655:Histone Deacetylases / Q000737:chemistry / Q000502:physiology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000378:metabolism*
D006877:Hydroxamic Acids; D016329:Sp1 Transcription Factor; C012589:trichostatin A; D008156:Luciferases; D019916:Choline-Phosphate Cytidylyltransferase; C500611:Pcyt1a protein, mouse; D006655:Histone Deacetylases