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T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2003 Oct 03; Vol. 278 (40), pp. 38586-92. Date of Electronic Publication: 2003 Jul 21. - Publication Year :
- 2003
-
Abstract
- Nuclear receptors (NR) classically regulate gene expression by stimulating transcription upon binding to their cognate ligands. It is now well established that NR-mediated transcriptional activation requires the recruitment of coregulator complexes, which facilitate recruitment of the basal transcription machinery through direct interactions with the basal transcription machinery and/or through chromatin remodeling. However, a number of recently described NR coactivators have been implicated in cross-talk with other nuclear processes including RNA splicing and DNA repair. T:G mismatch-specific thymine DNA glycosylase (TDG) is required for base excision repair of deaminated methylcytosine. Here we show that TDG is a coactivator for estrogen receptor alpha (ERalpha). We demonstrate that TDG interacts with ERalpha in vitro and in vivo and suggest a separate role for TDG to its established role in DNA repair. We show that this involves helix 12 of ERalpha. The region of interaction in TDG is mapped to a putative alpha-helical motif containing a motif distinct from but similar to the LXXLL motif that mediates interaction with NR. Together with recent reports linking TFIIH in regulating NR function, our findings provide new data to further support an important link between DNA repair proteins and nuclear receptor function.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Animals
Base Pair Mismatch
COS Cells
Cell Nucleus metabolism
Chloramphenicol O-Acetyltransferase metabolism
Chromatin metabolism
DNA metabolism
DNA Glycosylases
DNA Repair
Estrogen Receptor alpha
Genetic Vectors
Glutathione Transferase metabolism
Humans
Immunoblotting
Ligands
Models, Genetic
Molecular Sequence Data
Mutagenesis, Site-Directed
Precipitin Tests
Protein Binding
Protein Biosynthesis
RNA metabolism
RNA Splicing
Receptors, Estrogen metabolism
Recombinant Fusion Proteins metabolism
Sequence Homology, Amino Acid
Thymidine chemistry
Transcription, Genetic
Transcriptional Activation
Transfection
Two-Hybrid System Techniques
beta-Galactosidase metabolism
Estrogens metabolism
N-Glycosyl Hydrolases chemistry
Receptors, Estrogen chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 278
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12874288
- Full Text :
- https://doi.org/10.1074/jbc.M304286200