Structure-function analysis of the estrogen receptor α corepressor scaffold attachment factor-B1 -: Identification of a potent transcriptional repression domain
Structure-function analysis of the estrogen receptor α corepressor scaffold attachment factor-B1 -: Identification of a potent transcriptional repression domain
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DOI：
10.1074/jbc.m313726200
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发表时间：
2004-06-18
影响因子：
4.8
通讯作者：
Oesterreich, S
中科院分区：
文献类型：
--
作者：
Townson, SM;Kang, KY;Oesterreich, S
支架附着因子-B1（SAFB 1）是一种核基质蛋白，已被提出耦合染色质结构，转录和RNA加工。我们以前已经证明，SAFB 1可以抑制雌激素受体（ER α）介导的反式激活。在这里，我们提出了一个结构-功能的研究表明，反式激活是通过一个内在的和可转移的C-末端抑制结构域（RD）介导的。在家族成员SAFB 2中发现了类似的C-末端RD。从SAFB 1中去除RD导致显性负性SAFB 1蛋白增加配体依赖性和非依赖性ER α活性。SAFB 1 RD介导的阻遏部分阻断组蛋白脱乙酰酶抑制剂，但是，没有组蛋白脱乙酰酶抑制剂被确定在酵母双杂交筛选使用RD作为诱饵。相反，SAFB 1 RD被发现与TAFII 68相互作用，TAFII 68是基础转录机制的成员。我们提出了一个模型，其中SAFB 1抑制ER α活性通过间接关联与组蛋白脱乙酰化和相互作用的基础转录机制。
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.