Retinoic Acid Receptors Interact Physically and Functionally with the T:G Mismatch-specific Thymine-DNA Glycosylase

• DOI: 10.1074/jbc.273.33.20728
• Publication Date: 2002-07-26T14:56:47Z
• Authors: Soojong Um; Matthias Harbers; Arndt Benecke; Benoı̂t Pierrat; Régine Losson; Pierre Chambon
• Keywords: Transcriptional Activation; 0301 basic medicine; Endodeoxyribonucleases; Guanine; Base Sequence; Sequence Homology, Amino Acid; Receptors, Retinoic Acid; RNA Splicing; Molecular Sequence Data; Nucleic Acid Heteroduplexes; Recombinant Proteins; Deoxyribonuclease (Pyrimidine Dimer); Mice; 03 medical and health sciences; Animals; Amino Acid Sequence; Thymine; Protein Binding

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.