Histone deacetylase 1 can repress transcription by binding to Sp1

The members of the Sp1 transcription factor family can act as both negative and positive regulators of gene expression. Here we show that Sp1 can be a target for histone deacetylase 1 (HDAC1)-mediated transcriptional repressi on. The histone deacetylase inhibitor trichostatin A activates the chromoso mally integrated murine: thymidine kinase promoter in an Sp1-dependent mann er. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 ce lls demonstrate that Sp1 and HDAC1 can be part of the same complex. The int eraction between Sp1 and HDAC1 is direct and requires the carboxy-terminal domain of Sp1. Previously we have shown that the C terminus of Sp1 is neces sary for the interaction with the transcription factor E2F1 (J. Karlseder, H. Rotheneder, and E. Wintersberger, Mol. Cell. Biol. 16:1659-1667, 1996). Coexpression of E2F1 interferes with HDAC1 binding to Sp1 and abolishes Sp1 -mediated transcriptional repression. Our results indicate that one compone nt of Sp1-dependent gene regulation involves competition between the transc riptional repressor HDAC1 and the transactivating factor E2F1.