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 repression. The histone deacetylase inhibitor trichostatin A activates the chromosomally integrated murine thymidine kinase promoter in an Sp1-dependent manner. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex. The interaction 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 necessary 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 component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1.
Institute of Molecular Biology, Vienna Biocenter, University of Vienna, Vienna, Austria.
A
A
Doetzlhofer
H
H
Rotheneder
G
G
Lagger
M
M
Koranda
V
V
Kurtev
G
G
Brosch
E
E
Wintersberger
C
C
Seiser
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016192:Resting Phase, Cell Cycle; D056465:Retinoblastoma-Binding Protein 1; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D006657:Histones; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D016329:Sp1 Transcription Factor; D050680:Transcription Factor DP1; D014157:Transcription Factors; D013937:Thymidine Kinase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases