2004/06/01 by Steven M. Townson, Kaiyan Kang, Adrian V. Lee +1 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Genomics and Chromatin Dynamics #Estrogen and related hormone effects #Reproductive Biology and Fertility
paper · pdf · doi:10.1074/jbc.m313726200
openalex publication_date 2004/06/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/04
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.