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.