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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_5 http://www.w3.org/ns/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. http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/16204248 http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/16204248 http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#_5 http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ#pubinfo http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ http://purl.org/dc/terms/created 2014-07-03T14:30:38.425+02:00 http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAc2u2WVHzAe3HQMSI2WWxs5gPViTygoxlNHZ7fbceTjQ http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234