title: Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases.
abstract: Histone acetyltransferases and deacetylases are recruited by transcription factors and adapter proteins to regulate specific subsets of target genes. We were interested in identifying interaction partners of histone deacetylase 1 (HDAC1) that might be involved in conferring target or substrate specificity. Using the yeast two-hybrid system, we isolated the repressor of estrogen receptor activity (REA) as a novel HDAC1-associated protein. We demonstrated the in vivo interaction of REA with HDAC1 and characterized the respective domains required for their interaction in vitro. In addition, we found that REA also associates with the class II histone deacetylase HDAC5. In luciferase reporter assays, REA decreased transcription, and this repression was sensitive to the deacetylase inhibitor trichostatin A. Finally, we showed that REA specifically interacts with the chicken ovalbumin upstream binding transcription factors and II. The nuclear receptor chicken ovalbumin upstream binding transcription factor I was found to cooperate with REA and histone deacetylases in the repression of target genes. We, therefore, propose a novel function for REA as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases.
authors.affiliation: Institute of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Kurtev
authors.forename: Raphael
authors.initials: R
authors.lastname: Margueron
authors.forename: Karin
authors.initials: K
authors.lastname: Kroboth
authors.forename: Egon
authors.initials: E
authors.lastname: Ogris
authors.forename: Vincent
authors.initials: V
authors.lastname: Cavailles
authors.forename: Christian
authors.initials: C
authors.lastname: Seiser
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D051836:COUP Transcription Factors; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D000091402:Prohibitins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000378:metabolism*; D011987:Receptors, Steroid; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D012097:Repressor Proteins; D014157:Transcription Factors; C012589:trichostatin A; D008156:Luciferases; D005982:Glutathione Transferase; C404500:HDAC5 protein, human; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases