The N termini of friend of GATA (FOG) proteins define a novel transcriptional repression motif and a superfamily of transcriptional repressors
The N termini of friend of GATA (FOG) proteins define a novel transcriptional repression motif and a superfamily of transcriptional repressors
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DOI：
10.1074/jbc.m411240200
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发表时间：
2004-12-31
影响因子：
4.8
通讯作者：
Svensson, EC
中科院分区：
文献类型：
--
作者：
Lin, AC;Roche, AE;Svensson, EC
加塔之友（FOG）转录辅因子家族的成员是心血管和造血系统发育所必需的。FOG蛋白与转录激活因子的加塔家族成员物理相互作用并调节其活性。我们以前已经表明，FOG-2可以结合到GATA 4的N-末端锌指，并通过这种相互作用，抑制GATA 4介导的各种心脏启动子的转录激活。在这份报告中，我们进一步表征了抑制GATA 4转录活性所必需的FOG-2结构域。我们发现，FOG-2介导的阻遏不被组蛋白去乙酰化酶抑制剂tricostatin A阻断，表明FOG-2阻遏GATA 4通过组蛋白去乙酰化酶独立机制发生。FOG-2的N-末端缺失突变体揭示了FOG-2的前12个氨基酸是FOG-2介导的阻遏所必需的。这12个氨基酸与GAL 4的DNA结合结构域的融合表明，即使当募集到异源启动子时，该区域也足以介导转录抑制。FOG-2的N-末端结构域内的单个氨基酸取代将关键氨基酸序列定义为RRKQxxPxxI。有趣的是，NCBI蛋白质数据库的搜索确定了其他几个部分特征的锌指转录抑制因子，从各种脊椎动物物种，在其N末端含有这个基序。总之，这些观察定义了一个新的转录抑制基序和锌指转录抑制因子的超家族。
Members of the Friend of GATA (FOG) family of transcriptional co-factors are required for the development of both the cardiovascular and hematopoietic systems. FOG proteins physically interact with members of the GATA family of transcriptional activators and modulate their activity. We have previously shown that FOG-2 can bind to the N-terminal zinc finger of GATA4 and, via this interaction, repress GATA4-mediated transcriptional activation of various cardiac promoters. In this report we further characterize the domain of FOG-2 necessary for repression of GATA4 transcriptional activity. We show that FOG-2-mediated repression is not blocked by the histone deacetylase inhibitor tricostatin A, suggesting that FOG-2 repression of GATA4 occurs via a histone deacetylase independent mechanism. N-terminal deletion mutants of FOG-2 revealed that the first 12 amino acids of FOG-2 are necessary for FOG-2-mediated repression. Fusion of these 12 amino acids to the DNA binding domain of GAL4 demonstrated that this region is sufficient to mediate transcriptional repression even when recruited to a heterologous promoter. Single amino acid substitutions within this N-terminal domain of FOG-2 defined the critical amino acid sequence as RRKQxxPxxI. Interestingly, a search of the NCBI protein data base identified several other partially characterized zinc finger transcriptional repressors from various vertebrate species that contained this motif at their N terminus. Taken together, these observations define a novel transcriptional repression motif and a superfamily of zinc finger transcriptional repressors.