Doetzlhofer A, Rotheneder H, Lagger G, Koranda M, Kurtev V, Brosch G, Wintersberger E, Seiser C
Institute of Molecular Biology, Vienna Biocenter, University of Vienna, Vienna, Austria.
Mol Cell Biol. 1999 Aug;19(8):5504-11. doi: 10.1128/MCB.19.8.5504.
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.
Sp1转录因子家族的成员可作为基因表达的负调控因子和正调控因子。在此我们表明，Sp1可能是组蛋白去乙酰化酶1（HDAC1）介导的转录抑制作用的靶点。组蛋白去乙酰化酶抑制剂曲古抑菌素A以Sp1依赖的方式激活染色体整合的小鼠胸苷激酶启动子。用瑞士3T3成纤维细胞和293细胞进行的免疫共沉淀实验表明，Sp1和HDAC1可能是同一复合物的组成部分。Sp1与HDAC1之间的相互作用是直接的，且需要Sp1的羧基末端结构域。此前我们已表明，Sp1的C末端对于与转录因子E2F1的相互作用是必需的（J. Karlseder、H. Rotheneder和E. Wintersberger，《分子细胞生物学》16:1659 - 1667，1996年）。E2F1的共表达会干扰HDAC1与Sp1的结合，并消除Sp1介导的转录抑制作用。我们的结果表明，Sp1依赖的基因调控的一个组成部分涉及转录抑制因子HDAC1与反式激活因子E2F1之间的竞争。
