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All rights reserved." } ], "http://purl.org/dc/elements/1.1/title" : [ { "@value" : "BEL Framework Large Corpus Document" } ], "http://purl.org/pav/authoredBy" : [ { "@id" : "http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_6" } ], "http://purl.org/pav/version" : [ { "@value" : "1.4" } ] }, { "@id" : "http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_5", "http://www.w3.org/ns/prov#value" : [ { "@value" : "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. 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