Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription.
Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription.
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DOI：
10.1016/j.bbagrm.2016.01.005
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Martinez E
中科院分区：
文献类型：
--
作者：
Xu M;Gonzalez-Hurtado E;Martinez E
增强子的基因特异性激活涉及它们与核心启动子处的基础RNA聚合酶II转录机器的通信。核心启动子是多样的，并且可以含有各种序列元件，例如TATA盒、起始子（INR）和下游启动子元件（DPE），其分别被TFIID复合物的TATA结合蛋白（TBP）和TBP相关因子识别。核心启动子元件有助于增强子的基因选择性，并且已经鉴定了INR/DPE特异性增强子和激活子。在这里，我们确定了一个TATA盒选择性激活序列的人β-肌动蛋白（ACTB）基因的上游，介导血清反应因子（SRF）诱导的转录TATA依赖性启动子，但不依赖INR，并需要TBP的TATA结合/弯曲活性，这是否则从TATA少启动子转录。SRF依赖性ACTB序列在TATA启动子上是立体特异性的，但以不依赖于方向的方式激活含有复合TATA/INR的启动子。更一般地说，我们表明，SRF调节基因的肌动蛋白/细胞骨架/收缩家庭往往有一个TATA盒。这些结果表明，TFIID介导的转录在哺乳动物细胞中的TATA依赖性和INR依赖性机制不同，仅与某些立体特异性的激活剂组合相容，并且TBP-TATA结合机制对于肌动蛋白/细胞因子相关基因家族的SRF激活是重要的。
Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.