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.
Mesh Terms:
Animals, Cell Line, Cell Line, Tumor, Enzyme Inhibitors, Genes, Dominant, Genetic Vectors, Hela Cells, Histone Deacetylase Inhibitors, Histones, Humans, Immunoblotting, Ligands, Luciferases, Matrix Attachment Region Binding Proteins, Mice, Models, Genetic, NIH 3T3 Cells, Nuclear Matrix-Associated Proteins, Plasmids, Protein Binding, Protein Structure, Tertiary, RNA, Receptors, Estrogen, Structure-Activity Relationship, Transcription, Genetic, Transcriptional Activation, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Jun. 18, 2004
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