Murine Sall1 represses transcription by recruiting a histone deacetylase complex
Murine Sall1 represses transcription by recruiting a histone deacetylase complex
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DOI：
10.1074/jbc.m200052200
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发表时间：
2002-04-26
影响因子：
4.8
通讯作者：
Rauchman, M
中科院分区：
文献类型：
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作者：
Kiefer, SM;McDill, BW;Rauchman, M
SAL家族的多锌指蛋白调控器官发生。来自果蝇的遗传学证据表明，Spalt(Sal)可以以细胞自主的方式改变基因表达，但Sal蛋白从未被直接分析过其激活或抑制转录的能力。在这份报告中，我们证明了SAL家族的一个成员，小鼠SALL1，是一个有效的转录抑制因子。当与异源DNA结合域融合时，SALL1可抑制荧光素酶报告基因的转录，抑制倍数超过100倍。如缺失分析所示，仅N末端的表达就足以进行剂量反应抑制，这需要蛋白质的极端N末端氨基酸。SALL1的N端相对于启动子可以在短距离和长距离进行抑制，用组蛋白去乙酰化酶(HDAC)抑制剂曲古抑素A处理后，抑制作用降低了3倍。抑制所需的相同蛋白质区域与染色质重塑复合体的成分HDAC1、HDAC2、RbAp46/48、MTA-1和MTA-2物理上相互作用。最后，我们证明了SALL1定位于离散的核焦点，并且这种定位依赖于N末端的阻遏结构域。综上所述，这些结果表明，小鼠SALL1的N端可以招募HDAC复合体来介导转录抑制。
The multi-zinc finger proteins of the Sal family regulate organogenesis. Genetic evidence from Drosophila has shown that spalt (sal) can alter gene expression in a cell autonomous fashion, but Sal proteins have never been directly analyzed for their ability to activate or repress transcription. In this report, we show that a member of the Sal family, mouse Sall1, is a potent transcriptional repressor. When fused to a heterologous DNA-binding domain, Sall1 represses transcription of a luciferase reporter by over 100-fold. Expression of the N terminus alone is sufficient for dose-responsive repression that, as shown by deletion analysis, requires the extreme N-terminal amino acids of the protein. The N terminus of Sall1 can repress at both short and long range relative to the promoter, and treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A, alleviates repression by 3-fold. The same regions of the protein that are required for repression physically interact with components of chromatin remodeling complexes, HDAC1, HDAC2, RbAp46/48, MTA-1, and MTA-2. Finally, we demonstrate that Sall1 is localized to discrete nuclear foci and this localization depends on the N-terminal repression domain. Together, these results suggest that the N terminus of mouse Sall1 can recruit HDAC complexes to mediate transcriptional repression.