Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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Cell Line, Tumor
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Enzyme Inhibitors / pharmacology
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Genes, Dominant
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Genetic Vectors
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HeLa Cells
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Histone Deacetylase Inhibitors
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Histones / metabolism
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Humans
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Immunoblotting
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Ligands
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Luciferases / metabolism
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Matrix Attachment Region Binding Proteins / chemistry*
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Matrix Attachment Region Binding Proteins / physiology*
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Mice
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Models, Genetic
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NIH 3T3 Cells
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Nuclear Matrix-Associated Proteins / chemistry*
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Nuclear Matrix-Associated Proteins / physiology*
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Plasmids / metabolism
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Protein Binding
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Protein Structure, Tertiary
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RNA / chemistry
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Receptors, Estrogen / chemistry*
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Receptors, Estrogen / physiology*
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Structure-Activity Relationship
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Transcription, Genetic
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Transcriptional Activation
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Transfection
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Two-Hybrid System Techniques
Substances
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Histones
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Ligands
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Matrix Attachment Region Binding Proteins
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Nuclear Matrix-Associated Proteins
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Receptors, Estrogen
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SAFB protein, human
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SAFB2 protein, human
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RNA
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Luciferases