TBP-like protein (TLP) interferes with Taspase1-mediated processing of TFIIA and represses TATA box gene expression.
TBP-like protein (TLP) interferes with Taspase1-mediated processing of TFIIA and represses TATA box gene expression.
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DOI：
10.1093/nar/gkv576
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发表时间：
2015-07-27
影响因子：
14.9
通讯作者：
Tamura TA
中科院分区：
文献类型：
--
作者：
Suzuki H;Isogai M;Maeda R;Ura K;Tamura TA
TBP-TFIIA相互作用参与TATA盒驱动的启动子的增强。TFIIA通过稳定TATA盒结合的TBP激活转录。TFIIA的前体经过Taspase 1定向加工产生α和β亚基。虽然这种处理已被假定为TFIIA的启动子激活功能所需的，很少有人知道如何处理的调节。在这项研究中，我们发现TBP-like蛋白（TLP），它具有最高的亲和力TFIIA已知的蛋白质，影响Taspase 1驱动的加工TFIIA。TLP干扰TFIIA加工在体内和体外，和直接结合的TLP TFIIA是必不可少的抑制加工。我们还表明，TATA盒启动子是专门加强处理TFIIA。处理的TFIIA，但不是未处理的TFIIA，与TATA盒相关。在TLR敲低条件下，不仅TATA盒结合的TFIIA的量显着增加，而且染色质结合的TBP的量也显着增加，从而刺激TATA盒介导的基因表达。因此，我们认为TLP作为TFIIA加工的负调节剂，通过阻止TFIIA成熟来抑制TFIIA支配和TATA依赖的基因表达。
TBP-TFIIA interaction is involved in the potentiation of TATA box-driven promoters. TFIIA activates transcription through stabilization of TATA box-bound TBP. The precursor of TFIIA is subjected to Taspase1-directed processing to generate α and β subunits. Although this processing has been assumed to be required for the promoter activation function of TFIIA, little is known about how the processing is regulated. In this study, we found that TBP-like protein (TLP), which has the highest affinity to TFIIA among known proteins, affects Taspase1-driven processing of TFIIA. TLP interfered with TFIIA processing in vivo and in vitro, and direct binding of TLP to TFIIA was essential for inhibition of the processing. We also showed that TATA box promoters are specifically potentiated by processed TFIIA. Processed TFIIA, but not unprocessed TFIIA, associated with the TATA box. In a TLP-knocked-down condition, not only the amounts of TATA box-bound TFIIA but also those of chromatin-bound TBP were significantly increased, resulting in the stimulation of TATA box-mediated gene expression. Consequently, we suggest that TLP works as a negative regulator of the TFIIA processing and represses TFIIA-governed and TATA-dependent gene expression through preventing TFIIA maturation.