Structure-Function Analysis of the Estrogen Receptor Corepressor Scaffold Attachment Factor-B1

نویسندگان

  • Steven M. Townson
  • Kaiyan Kang
  • Adrian V. Lee
  • Steffi Oesterreich
چکیده

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 (ER )-mediated transactivation. Here we present a structure-function study showing that transactivation is mediated via an intrinsic and transferable Cterminal 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 ER 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 ER activity via indirect association with histone deacetylation and interaction with the basal transcription machinery.

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تاریخ انتشار 2004