PubMed:16204248 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/16204248","sourcedb":"PubMed","sourceid":"16204248","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/16204248","text":"TIS7 regulation of the beta-catenin/Tcf-4 target gene osteopontin (OPN) is histone deacetylase-dependent.\n12-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.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":105},"obj":"Sentence"},{"id":"T2","span":{"begin":106,"end":274},"obj":"Sentence"},{"id":"T3","span":{"begin":275,"end":355},"obj":"Sentence"},{"id":"T4","span":{"begin":356,"end":523},"obj":"Sentence"},{"id":"T5","span":{"begin":524,"end":696},"obj":"Sentence"},{"id":"T6","span":{"begin":697,"end":869},"obj":"Sentence"},{"id":"T7","span":{"begin":870,"end":987},"obj":"Sentence"},{"id":"T8","span":{"begin":988,"end":1119},"obj":"Sentence"},{"id":"T9","span":{"begin":1120,"end":1203},"obj":"Sentence"},{"id":"T10","span":{"begin":1204,"end":1372},"obj":"Sentence"},{"id":"T11","span":{"begin":1373,"end":1504},"obj":"Sentence"},{"id":"T12","span":{"begin":1505,"end":1749},"obj":"Sentence"},{"id":"T13","span":{"begin":1750,"end":2005},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"},{"subj":"T12","pred":"source","obj":"sentences"},{"subj":"T13","pred":"source","obj":"sentences"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":419,"end":425},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"T2","span":{"begin":452,"end":458},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"T3","span":{"begin":683,"end":689},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"T4","span":{"begin":1926,"end":1932},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T2","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T3","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T4","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":631,"end":637},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"}]},{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20053848","span":{"begin":1204,"end":1370},"obj":"p(MGI:Ifrd1) decreases r(MGI:Myc)"},{"id":"BEL:20053854","span":{"begin":988,"end":1118},"obj":"p(MGI:Ifrd1) decreases r(MGI:Spp1)"}],"attributes":[{"subj":"BEL:20053848","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20053854","pred":"source","obj":"2015-BEL-Sample-2"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":419,"end":425},"obj":"Body_part"},{"id":"T2","span":{"begin":452,"end":458},"obj":"Body_part"},{"id":"T3","span":{"begin":683,"end":689},"obj":"Body_part"},{"id":"T4","span":{"begin":1926,"end":1932},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"A4","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"},{"subj":"T3","pred":"source","obj":"Anatomy-MAT"},{"subj":"T4","pred":"source","obj":"Anatomy-MAT"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":67,"end":70},"obj":"Disease"},{"id":"T2","span":{"begin":404,"end":410},"obj":"Disease"},{"id":"T3","span":{"begin":537,"end":540},"obj":"Disease"},{"id":"T4","span":{"begin":631,"end":637},"obj":"Disease"},{"id":"T5","span":{"begin":697,"end":700},"obj":"Disease"},{"id":"T6","span":{"begin":919,"end":922},"obj":"Disease"},{"id":"T7","span":{"begin":1039,"end":1042},"obj":"Disease"},{"id":"T8","span":{"begin":1096,"end":1099},"obj":"Disease"},{"id":"T9","span":{"begin":1368,"end":1371},"obj":"Disease"},{"id":"T10","span":{"begin":1745,"end":1748},"obj":"Disease"},{"id":"T11","span":{"begin":1851,"end":1854},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0044690"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T4","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"},{"subj":"T6","pred":"source","obj":"mondo_disease"},{"subj":"T7","pred":"source","obj":"mondo_disease"},{"subj":"T8","pred":"source","obj":"mondo_disease"},{"subj":"T9","pred":"source","obj":"mondo_disease"},{"subj":"T10","pred":"source","obj":"mondo_disease"},{"subj":"T11","pred":"source","obj":"mondo_disease"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":392,"end":396},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1232,"end":1237},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"10088"},{"id":"A2","pred":"db_id","subj":"T2","obj":"10088"},{"id":"A3","pred":"db_id","subj":"T2","obj":"10090"},{"subj":"T1","pred":"source","obj":"NCBITAXON"},{"subj":"T2","pred":"source","obj":"NCBITAXON"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":419,"end":425},"obj":"Body_part"},{"id":"T3","span":{"begin":452,"end":458},"obj":"Body_part"},{"id":"T5","span":{"begin":459,"end":473},"obj":"Body_part"},{"id":"T6","span":{"begin":504,"end":513},"obj":"Body_part"},{"id":"T7","span":{"begin":564,"end":570},"obj":"Body_part"},{"id":"T8","span":{"begin":683,"end":695},"obj":"Body_part"},{"id":"T9","span":{"begin":1238,"end":1259},"obj":"Body_part"},{"id":"T10","span":{"begin":1926,"end":1932},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0001630"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0005090"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0001630"},{"id":"A4","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0005090"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL_0000514"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000056"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL_0000084"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL_0000187"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL_2000042"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0001630"},{"id":"A11","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0005090"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T6","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T7","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T8","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T9","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T10","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"Glycosmos15-CL","denotations":[{"id":"T1","span":{"begin":459,"end":473},"obj":"Cell"},{"id":"T2","span":{"begin":504,"end":513},"obj":"Cell"},{"id":"T3","span":{"begin":564,"end":570},"obj":"Cell"},{"id":"T4","span":{"begin":683,"end":695},"obj":"Cell"},{"id":"T5","span":{"begin":1238,"end":1259},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000514"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000056"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000187"},{"id":"A5","pred":"cl_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL:2000042"},{"subj":"T1","pred":"source","obj":"Glycosmos15-CL"},{"subj":"T2","pred":"source","obj":"Glycosmos15-CL"},{"subj":"T3","pred":"source","obj":"Glycosmos15-CL"},{"subj":"T4","pred":"source","obj":"Glycosmos15-CL"},{"subj":"T5","pred":"source","obj":"Glycosmos15-CL"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#ceec93","default":true},{"id":"Glycosmos6-MAT","color":"#ec93e8"},{"id":"PubmedHPO","color":"#93ecd6"},{"id":"2015-BEL-Sample-2","color":"#ecbc93"},{"id":"Anatomy-MAT","color":"#a293ec"},{"id":"mondo_disease","color":"#9eec93"},{"id":"NCBITAXON","color":"#ec93b8"},{"id":"Anatomy-UBERON","color":"#93d2ec"},{"id":"Glycosmos15-CL","color":"#ecec93"}]}]}}