title: The ETS family member TEL binds to nuclear receptors RAR and RXR and represses gene activation.
abstract: Retinoic acid receptor (RAR) signaling is important for regulating transcriptional activity of genes involved in growth, differentiation, metabolism and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a member of the ETS family of transcription factors, is a DNA-binding transcriptional repressor. Here, we identify TEL as a transcriptional repressor of RAR signaling by its direct binding to both RAR and its dimerisation partner, the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in two isoforms, created by the use of an alternative startcodon at amino acid 43. Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form of TEL represses RAR signaling much more efficiently. Binding studies revealed that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have shown that repression by TEL does not involve recruitment of histone deacetylases and suggest that polycomb group proteins participate in the process.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Magda A
authors.initials: MA
authors.lastname: Meester-Smoor
authors.forename: Marjolein J F W
authors.initials: MJ
authors.lastname: Janssen
authors.forename: W Martijn
authors.initials: WM
authors.lastname: ter Haar
authors.forename: Karel H M
authors.initials: KH
authors.lastname: van Wely
authors.forename: Albert-Jan L H J
authors.initials: AJ
authors.lastname: Aarnoudse
authors.forename: Gertine
authors.initials: G
authors.lastname: van Oord
authors.forename: Gabrielle B A
authors.initials: GB
authors.lastname: van Tilburg
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
mesh_terms: D017398:Alternative Splicing; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D019077:Helix-Turn-Helix Motifs / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D047468:Immunoprecipitation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008156:Luciferases; D020033:Protein Isoforms; D050783:Proto-Oncogene Proteins c-ets; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D000097764:ETS Translocation Variant 6 Protein; C000607071:RARA protein, human; C012589:trichostatin A