Retinoic acid receptors interact physically and functionally with the T:G mismatch-specific thymine-DNA glycosylase.
The pleiotropic effects of retinoids are mediated by nuclear receptors that are activated by 9-cis- or all-trans-retinoic acid to function as ligand-dependent transcription factors. In a yeast one-hybrid screen for proteins capable of interacting with native retinoic acid receptor (RAR), we have isolated the T:G mismatch-specific thymine-DNA glycosylase (TDG), which initiates the repair of T:G mismatches caused by spontaneous deamination of methylated cytosines. Here, we report that TDG can interact with RAR and the retinoid X receptor (RXR) in a ligand-independent manner, both in yeast and in vitro. Mapping of the binding sites revealed interaction with a region of the ligand binding domain harboring alpha-helix 1 in both RAR and RXR. In transient transfection experiments, TDG potentiated transactivation by RXR from a direct repeat element spaced by one nucleotide (DR1) and by RXR/RAR heterodimers from a direct repeat element spaced by five nucleotides (DR5). In vitro, TDG enhanced RXR and RXR/RAR binding to their response elements. These data indicate that TDG is not only a repair enzyme, but could also function in the control of transcription.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163, 67404 Illkirch Cedex, France.
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Harbers
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Benecke
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Pierrat
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Losson
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Chambon
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D006147:Guanine; D051379:Mice; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes; D011485:Protein Binding; D012326:RNA Splicing; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013941:Thymine; D015533:Transcriptional Activation
D009692:Nucleic Acid Heteroduplexes; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D006147:Guanine; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); D013941:Thymine