title: The leukemia-associated gene TEL encodes a transcription repressor which associates with SMRT and mSin3A.
abstract: The E-26 transforming specific (ETS)-related gene TEL, also known as ETV6, encodes a strong transcription repressor that is rearranged in several recurring chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. The TEL protein contains two functional domains that have been partially characterized: a helix-loop-helix (HLH) domain (also known as a pointed domain) at the N-terminus, which physically interacts with itself, with the SUMO-conjugating enzyme UBC9, and with FLI1; and, at the C-terminus, an ETS domain with DNA-binding properties. Little is known about the function of the central region of TEL. The HLH domain and the central region of TEL are consistently maintained in the t(12;21), which is the most frequent chromosomal translocation involving TEL. In this study, we found that the HLH domain and the central region of TEL mediate transcription repression by two distinct mechanisms. The central region involves the recruitment of a repression complex, including SMRT and mSin3A. The HLH domain represses gene transcription through a mechanism that is independent of known corepressors. Thus, TEL belongs to a growing number of transcription factors rearranged by chromosomal translocations that are associated with the corepressor complexes.
authors.affiliation: Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, 60153, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Chakrabarti
authors.forename: G
authors.initials: G
authors.lastname: Nucifora
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D056985:Nuclear Receptor Co-Repressor 2; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D056985:Nuclear Receptor Co-Repressor 2; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C539130:NCOR2 protein, human; C539131:Ncor2 protein, mouse; C099683:SIN3A transcription factor