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.
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
Claudia
C
Banchio
Susanne
S
Lingrell
Dennis E
DE
Vance
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