Structure-function analysis of the estrogen receptor alpha corepressor scaffold attachment factor-B1: identification of a potent transcriptional repression domain.
Scaffold attachment factor-B1 (SAFB1) is a nuclear matrix protein that has been proposed to couple chromatin structure, transcription, and RNA processing. We have previously shown that SAFB1 can repress estrogen receptor (ERalpha)-mediated transactivation. Here we present a structure-function study showing that transactivation is mediated via an intrinsic and transferable C-terminal repression domain (RD). A similar C-terminal RD was found in the family member SAFB2. Removal of the RD from SAFB1 resulted in a dominant-negative SAFB1 protein that increased ligand-dependent and -independent ERalpha activity. SAFB1RD-mediated repression was partly blocked by histone deacetylase inhibitors; however, no histone deacetylase inhibitors were identified in a yeast two-hybrid screen using the RD as bait. Instead, SAFB1RD was found to interact with TAFII68, a member of the basal transcription machinery. We propose a model in which SAFB1 represses ERalpha activity via indirect association with histone deacetylation and interaction with the basal transcription machinery.
Townson
Steven M
SM
Departments of Medicine, The Breast Center, Baylor College of Medicine and Methodist Hospital, Houston, Texas 77030, USA.
Kang
Kaiyan
K
Lee
Adrian V
AV
Oesterreich
Steffi
S
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D005822:Genetic Vectors; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D051379:Mice; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry* / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D008024:Ligands; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D011960:Receptors, Estrogen; C109132:SAFB protein, human; C486369:SAFB2 protein, human; D012313:RNA; D008156:Luciferases