sub:provenance {
beldoc: dce:description "Approximately 61,000 statements." ;
dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved." ;
dce:title "BEL Framework Large Corpus Document" ;
pav:authoredBy sub:_6 ;
pav:version "1.4" .
sub:_5 prov: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. 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." ;
prov:wasQuotedFrom pubmed:16204248 .
sub:_6 rdfs:label "Selventa" .
sub:assertion prov:hadPrimarySource pubmed:16204248 ;
prov:wasDerivedFrom beldoc: ,
sub:_5 .
}