PubMed:12588862 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/12588862","sourcedb":"PubMed","sourceid":"12588862","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/12588862","text":"The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6).\nH-L(3)MBT, the human homolog of the Drosophila lethal(3)malignant brain tumor protein, is a member of the polycomb group (PcG) of proteins, which function as transcriptional regulators in large protein complexes. Homozygous mutations in the l(3)mbt gene cause brain tumors in Drosophila, identifying l(3)mbt as a tumor suppressor gene. The h-l(3)mbt gene maps to chromosome 20q12, within a common deleted region associated with myeloid hematopoietic malignancies. H-L(3)MBT contains three repeats of 100 residues called MBT repeats, whose function is unknown, and a C-terminal alpha-helical structure, the SPM (SCM, PH, MBT domain, which is structurally similar to the SAM (sterile alpha motif) protein-protein interaction domain, found in several ETS transcription factors, including TEL (translocation Ets leukemia). We report that H-L(3)MBT is a transcriptional repressor and that its activity is largely dependent on the presence of a region containing the three MBT repeats. H-L(3)MBT acts as a histone deacetylase-independent transcriptional repressor, based on its lack of sensitivity to trichostatin A. We found that H-L(3)MBT binds in vivo to TEL, and we have mapped the region of interaction to their respective SPM/SAM domains. We show that the ability of TEL to repress TEL-responsive promoters is enhanced by the presence of H-L(3)MBT, an effect dependent on the H-L(3)MBT and the TEL interacting domains. These experiments suggest that histone deacetylase-independent transcriptional repression by TEL depends on the recruitment of PcG proteins. We speculate that the interaction of TEL with H-L(3)MBT can direct a PcG complex to genes repressed by TEL, stabilizing their repressed state.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":131,"end":140},"obj":"gene:26013"},{"id":"T1","span":{"begin":187,"end":208},"obj":"disease:C0750979"},{"id":"T2","span":{"begin":131,"end":140},"obj":"gene:26013"},{"id":"T3","span":{"begin":187,"end":208},"obj":"disease:C0153633"},{"id":"T4","span":{"begin":372,"end":379},"obj":"gene:83746"},{"id":"T5","span":{"begin":391,"end":403},"obj":"disease:C0006118"},{"id":"T6","span":{"begin":372,"end":379},"obj":"gene:26013"},{"id":"T7","span":{"begin":391,"end":403},"obj":"disease:C0006118"},{"id":"T8","span":{"begin":471,"end":480},"obj":"gene:26013"},{"id":"T9","span":{"begin":567,"end":593},"obj":"disease:C0376544"},{"id":"T10","span":{"begin":595,"end":604},"obj":"gene:26013"},{"id":"T11","span":{"begin":939,"end":947},"obj":"disease:C0023418"},{"id":"T12","span":{"begin":651,"end":654},"obj":"gene:5657"},{"id":"T13","span":{"begin":939,"end":947},"obj":"disease:C0023418"},{"id":"T14","span":{"begin":751,"end":754},"obj":"gene:5657"},{"id":"T15","span":{"begin":939,"end":947},"obj":"disease:C0023418"},{"id":"T16","span":{"begin":916,"end":919},"obj":"gene:2120"},{"id":"T17","span":{"begin":939,"end":947},"obj":"disease:C0023418"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"},{"id":"R8","pred":"associated_with","subj":"T14","obj":"T15"},{"id":"R9","pred":"associated_with","subj":"T16","obj":"T17"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"},{"subj":"T12","pred":"source","obj":"DisGeNET"},{"subj":"T13","pred":"source","obj":"DisGeNET"},{"subj":"T14","pred":"source","obj":"DisGeNET"},{"subj":"T15","pred":"source","obj":"DisGeNET"},{"subj":"T16","pred":"source","obj":"DisGeNET"},{"subj":"T17","pred":"source","obj":"DisGeNET"}]},{"project":"relna","denotations":[{"id":"T1","span":{"begin":14,"end":17},"obj":"Protein"},{"id":"T2","span":{"begin":119,"end":122},"obj":"DNA"},{"id":"T3","span":{"begin":124,"end":128},"obj":"DNA"},{"id":"T4","span":{"begin":131,"end":140},"obj":"DNA"},{"id":"T5","span":{"begin":178,"end":208},"obj":"Protein"},{"id":"T6","span":{"begin":376,"end":379},"obj":"Protein"},{"id":"T7","span":{"begin":435,"end":438},"obj":"Protein"},{"id":"T8","span":{"begin":471,"end":480},"obj":"DNA"},{"id":"T9","span":{"begin":595,"end":604},"obj":"DNA"},{"id":"T10","span":{"begin":651,"end":654},"obj":"Protein"},{"id":"T11","span":{"begin":916,"end":919},"obj":"DNA"},{"id":"T12","span":{"begin":921,"end":947},"obj":"DNA"},{"id":"T13","span":{"begin":965,"end":974},"obj":"DNA"},{"id":"T14","span":{"begin":1098,"end":1101},"obj":"Protein"},{"id":"T15","span":{"begin":1111,"end":1120},"obj":"DNA"},{"id":"T16","span":{"begin":1256,"end":1265},"obj":"DNA"},{"id":"T17","span":{"begin":1283,"end":1286},"obj":"DNA"},{"id":"T18","span":{"begin":1398,"end":1401},"obj":"DNA"},{"id":"T19","span":{"begin":1413,"end":1416},"obj":"DNA"},{"id":"T20","span":{"begin":1469,"end":1478},"obj":"DNA"},{"id":"T21","span":{"begin":1507,"end":1516},"obj":"DNA"},{"id":"T22","span":{"begin":1643,"end":1646},"obj":"DNA"},{"id":"T23","span":{"begin":1728,"end":1731},"obj":"DNA"},{"id":"T24","span":{"begin":1737,"end":1746},"obj":"DNA"},{"id":"T25","span":{"begin":1794,"end":1797},"obj":"DNA"}],"relations":[{"id":"R0","pred":"linked","subj":"T1","obj":"T2"},{"id":"R1","pred":"linked","subj":"T1","obj":"T3"}],"attributes":[{"subj":"T1","pred":"source","obj":"relna"},{"subj":"T2","pred":"source","obj":"relna"},{"subj":"T3","pred":"source","obj":"relna"},{"subj":"T4","pred":"source","obj":"relna"},{"subj":"T5","pred":"source","obj":"relna"},{"subj":"T6","pred":"source","obj":"relna"},{"subj":"T7","pred":"source","obj":"relna"},{"subj":"T8","pred":"source","obj":"relna"},{"subj":"T9","pred":"source","obj":"relna"},{"subj":"T10","pred":"source","obj":"relna"},{"subj":"T11","pred":"source","obj":"relna"},{"subj":"T12","pred":"source","obj":"relna"},{"subj":"T13","pred":"source","obj":"relna"},{"subj":"T14","pred":"source","obj":"relna"},{"subj":"T15","pred":"source","obj":"relna"},{"subj":"T16","pred":"source","obj":"relna"},{"subj":"T17","pred":"source","obj":"relna"},{"subj":"T18","pred":"source","obj":"relna"},{"subj":"T19","pred":"source","obj":"relna"},{"subj":"T20","pred":"source","obj":"relna"},{"subj":"T21","pred":"source","obj":"relna"},{"subj":"T22","pred":"source","obj":"relna"},{"subj":"T23","pred":"source","obj":"relna"},{"subj":"T24","pred":"source","obj":"relna"},{"subj":"T25","pred":"source","obj":"relna"}]},{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":130},"obj":"Sentence"},{"id":"T2","span":{"begin":131,"end":343},"obj":"Sentence"},{"id":"T3","span":{"begin":344,"end":466},"obj":"Sentence"},{"id":"T4","span":{"begin":467,"end":594},"obj":"Sentence"},{"id":"T5","span":{"begin":595,"end":949},"obj":"Sentence"},{"id":"T6","span":{"begin":950,"end":1110},"obj":"Sentence"},{"id":"T7","span":{"begin":1111,"end":1241},"obj":"Sentence"},{"id":"T8","span":{"begin":1242,"end":1369},"obj":"Sentence"},{"id":"T9","span":{"begin":1370,"end":1549},"obj":"Sentence"},{"id":"T10","span":{"begin":1550,"end":1690},"obj":"Sentence"},{"id":"T11","span":{"begin":1691,"end":1833},"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"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":4,"end":9},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":146,"end":151},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":167,"end":177},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":407,"end":417},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2081351"},{"id":"A4","pred":"db_id","subj":"T3","obj":"32281"},{"id":"A5","pred":"db_id","subj":"T3","obj":"7215"},{"id":"A6","pred":"db_id","subj":"T6","obj":"2081351"},{"id":"A7","pred":"db_id","subj":"T6","obj":"32281"},{"id":"A8","pred":"db_id","subj":"T6","obj":"7215"},{"subj":"T1","pred":"source","obj":"NCBITAXON"},{"subj":"T2","pred":"source","obj":"NCBITAXON"},{"subj":"T3","pred":"source","obj":"NCBITAXON"},{"subj":"T6","pred":"source","obj":"NCBITAXON"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"12588862-1#0#9#gene26013","span":{"begin":131,"end":140},"obj":"gene26013"},{"id":"12588862-1#56#77#diseaseC0153633","span":{"begin":187,"end":208},"obj":"diseaseC0153633"},{"id":"12588862-2#28#35#gene26013","span":{"begin":372,"end":379},"obj":"gene26013"},{"id":"12588862-2#28#35#gene83746","span":{"begin":372,"end":379},"obj":"gene83746"},{"id":"12588862-2#87#94#gene26013","span":{"begin":431,"end":438},"obj":"gene26013"},{"id":"12588862-2#87#94#gene83746","span":{"begin":431,"end":438},"obj":"gene83746"},{"id":"12588862-2#47#59#diseaseC0006118","span":{"begin":391,"end":403},"obj":"diseaseC0006118"},{"id":"12588862-3#4#13#gene26013","span":{"begin":471,"end":480},"obj":"gene26013"},{"id":"12588862-3#100#126#diseaseC0376544","span":{"begin":567,"end":593},"obj":"diseaseC0376544"},{"id":"12588862-4#56#59#gene5657","span":{"begin":651,"end":654},"obj":"gene5657"},{"id":"12588862-4#156#159#gene5657","span":{"begin":751,"end":754},"obj":"gene5657"},{"id":"12588862-4#321#324#gene2120","span":{"begin":916,"end":919},"obj":"gene2120"},{"id":"12588862-4#344#352#diseaseC0023418","span":{"begin":939,"end":947},"obj":"diseaseC0023418"}],"relations":[{"id":"0#9#gene2601356#77#diseaseC0153633","pred":"associated_with","subj":"12588862-1#0#9#gene26013","obj":"12588862-1#56#77#diseaseC0153633"},{"id":"28#35#gene2601347#59#diseaseC0006118","pred":"associated_with","subj":"12588862-2#28#35#gene26013","obj":"12588862-2#47#59#diseaseC0006118"},{"id":"28#35#gene8374647#59#diseaseC0006118","pred":"associated_with","subj":"12588862-2#28#35#gene83746","obj":"12588862-2#47#59#diseaseC0006118"},{"id":"87#94#gene2601347#59#diseaseC0006118","pred":"associated_with","subj":"12588862-2#87#94#gene26013","obj":"12588862-2#47#59#diseaseC0006118"},{"id":"87#94#gene8374647#59#diseaseC0006118","pred":"associated_with","subj":"12588862-2#87#94#gene83746","obj":"12588862-2#47#59#diseaseC0006118"},{"id":"4#13#gene26013100#126#diseaseC0376544","pred":"associated_with","subj":"12588862-3#4#13#gene26013","obj":"12588862-3#100#126#diseaseC0376544"},{"id":"56#59#gene5657344#352#diseaseC0023418","pred":"associated_with","subj":"12588862-4#56#59#gene5657","obj":"12588862-4#344#352#diseaseC0023418"},{"id":"156#159#gene5657344#352#diseaseC0023418","pred":"associated_with","subj":"12588862-4#156#159#gene5657","obj":"12588862-4#344#352#diseaseC0023418"},{"id":"321#324#gene2120344#352#diseaseC0023418","pred":"associated_with","subj":"12588862-4#321#324#gene2120","obj":"12588862-4#344#352#diseaseC0023418"}],"attributes":[{"subj":"12588862-1#0#9#gene26013","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-1#56#77#diseaseC0153633","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-2#28#35#gene26013","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-2#28#35#gene83746","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-2#87#94#gene26013","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-2#87#94#gene83746","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-2#47#59#diseaseC0006118","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-3#4#13#gene26013","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-3#100#126#diseaseC0376544","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-4#56#59#gene5657","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-4#156#159#gene5657","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-4#321#324#gene2120","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12588862-4#344#352#diseaseC0023418","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":187,"end":208},"obj":"Disease"},{"id":"T2","span":{"begin":391,"end":403},"obj":"Disease"},{"id":"T3","span":{"begin":444,"end":449},"obj":"Disease"},{"id":"T4","span":{"begin":737,"end":740},"obj":"Disease"},{"id":"T5","span":{"begin":805,"end":812},"obj":"Disease"},{"id":"T6","span":{"begin":939,"end":947},"obj":"Disease"},{"id":"T7","span":{"begin":1353,"end":1356},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0001657"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0021211"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0010400"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005047"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005059"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0010400"},{"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"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":197,"end":202},"obj":"http://purl.obolibrary.org/obo/MAT_0000098"},{"id":"T2","span":{"begin":391,"end":396},"obj":"http://purl.obolibrary.org/obo/MAT_0000098"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T2","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":197,"end":202},"obj":"Body_part"},{"id":"T2","span":{"begin":391,"end":396},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000098"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000098"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":197,"end":202},"obj":"Body_part"},{"id":"T3","span":{"begin":391,"end":396},"obj":"Body_part"},{"id":"T5","span":{"begin":494,"end":504},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000955"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_6110636"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000955"},{"id":"A4","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_6110636"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/GO_0005694"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":197,"end":208},"obj":"Phenotype"},{"id":"T2","span":{"begin":391,"end":403},"obj":"Phenotype"},{"id":"T3","span":{"begin":444,"end":449},"obj":"Phenotype"},{"id":"T4","span":{"begin":939,"end":947},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0030692"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0030692"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0001909"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"},{"subj":"T3","pred":"source","obj":"HP-phenotype"},{"subj":"T4","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#ecd993","default":true},{"id":"relna","color":"#bf93ec"},{"id":"sentences","color":"#93eca5"},{"id":"NCBITAXON","color":"#ec939a"},{"id":"DisGeNET5_gene_disease","color":"#93b4ec"},{"id":"mondo_disease","color":"#ceec93"},{"id":"Glycosmos6-MAT","color":"#ec93e8"},{"id":"Anatomy-MAT","color":"#93ecd5"},{"id":"Anatomy-UBERON","color":"#ecbb93"},{"id":"HP-phenotype","color":"#a193ec"}]}]}}