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TIS7 regulation of the beta-catenin/Tcf-4 target gene osteopontin (OPN) is histone deacetylase-dependent.
Vietor, Ilja; Kurzbauer, Robert; Brosch, Gerald; Huber, Lukas A.
Afiliação
  • Vietor I; Biocenter, Division of Cell Biology, Medical University Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria.
J Biol Chem ; 280(48): 39795-801, 2005 Dec 02.
Article em En | MEDLINE | ID: mdl-16204248
12-O-Tetradecanoylphorbol-13-acetate-induced sequence 7 (TIS7) acts as a transcriptional co-repressor interacting with SIN3, the histone deacetylase-containing complex. The overexpression of TIS7 down-regulates expression of a specific set of genes. Homozygous deletion of this gene in mice delays injury-induced muscle regeneration and inhibits muscle satellite cell differentiation and fusion of myoblasts in vitro. Osteopontin (OPN), a known beta-catenin/T cell factor-4 (Tcf-4) downstream target gene, is up-regulated in tumors and in cells with increased motility such as muscle cells. OPN promoter sequence contains binding sites for Sp1, glucocorticoid receptor, E-box-binding factors, octamer motif-binding protein, c-Myc, and other transcription factors. Previously we have shown that TIS7 regulates the OPN expression through the inhibition of the Sp1-activating effects. Here we show that TIS7 has the capacity to inhibit OPN expression also through Lef-1, the second identified OPN regulatory element. TIS7 has the capacity to down-regulate beta-catenin/Tcf-4 transcriptional activity. TIS7 homologous deletion in mouse embryonic fibroblasts increased not only the TOPflash reporter gene transcriptional activity but also the expression of c-Myc and OPN. Furthermore, we show that TIS7 overexpression leads to the beta-catenin interaction with enzymatically active histone deacetylases. We propose that TIS7 down-regulates the beta-catenin/Tcf-4 transcriptional activity via its interaction with histone deacetylase-containing complex thereby inhibiting the expression of beta-catenin downstream target genes such as c-Myc and OPN. We hypothesize that TIS7 as a negative regulator of transcriptional activity represses expression of OPN and beta-catenin/Tcf-4 target genes, which are involved in myogenesis, muscle maintenance, and regeneration in a histone deacetylase dependent manner.
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sialoglicoproteínas / Regulação Enzimológica da Expressão Gênica / Proteínas Imediatamente Precoces / Beta Catenina / Fatores de Transcrição TCF / Histona Desacetilases / Proteínas de Membrana Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2005 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sialoglicoproteínas / Regulação Enzimológica da Expressão Gênica / Proteínas Imediatamente Precoces / Beta Catenina / Fatores de Transcrição TCF / Histona Desacetilases / Proteínas de Membrana Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2005 Tipo de documento: Article