The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Section of Molecular Biology, University of California, San Diego, La Jolla, CA, United States of America.
PLoS One. 2019 Apr 18;14(4):e0215695. doi: 10.1371/journal.pone.0215695. eCollection 2019.
The regulation of transcription initiation is critical for developmental and cellular processes. RNA polymerase II (Pol II) is recruited by the basal transcription machinery to the core promoter where Pol II initiates transcription. The core promoter encompasses the region from -40 to +40 bp relative to the +1 transcription start site (TSS). Core promoters may contain one or more core promoter motifs that confer specific properties to the core promoter, such as the TATA box, initiator (Inr) and motifs that are located downstream of the TSS, namely, motif 10 element (MTE), the downstream core promoter element (DPE) and the Bridge, a bipartite core promoter element. We had previously shown that Caudal, an enhancer-binding homeodomain transcription factor and a key regulator of the Hox gene network, is a DPE-specific activator. Interestingly, pair-rule proteins have been implicated in enhancer-promoter communication at the engrailed locus. Fushi tarazu (Ftz) is an enhancer-binding homeodomain transcription factor encoded by the ftz pair-rule gene. Ftz works in concert with its co-factor, Ftz-F1, to activate transcription. Here, we examined whether Ftz and Ftz-F1 activate transcription with a preference for a specific core promoter motif. Our analysis revealed that similarly to Caudal, Ftz and Ftz-F1 activate the promoter containing a TATA box mutation to significantly higher levels than the promoter containing a DPE mutation, thus demonstrating a preference for the DPE motif. We further discovered that Ftz target genes are enriched for a combination of functional downstream core promoter elements that are conserved among Drosophila species. Thus, the unique combination (Inr, Bridge and DPE) of functional downstream core promoter elements within Ftz target genes highlights the complexity of transcriptional regulation via the core promoter in the transcription of different developmental gene regulatory networks.
转录起始的调控对于发育和细胞过程至关重要。RNA 聚合酶 II（Pol II）被基本转录机制募集到核心启动子，在那里 Pol II 起始转录。核心启动子包含相对于+1 转录起始位点（TSS）的-40 到+40bp 的区域。核心启动子可能包含一个或多个核心启动子基序，这些基序赋予核心启动子特定的性质，例如 TATA 盒、起始子（Inr）和位于 TSS 下游的基序，即 10 元件（MTE）、下游核心启动子元件（DPE）和 Bridge，一个双部分核心启动子元件。我们之前曾表明，Caudal，一种增强子结合同源域转录因子，是 Hox 基因网络的关键调节剂，是 DPE 特异性激活子。有趣的是，pair-rule 蛋白已被牵连在 engrailed 基因座的增强子-启动子通讯中。Fushi tarazu（Ftz）是由 ftz pair-rule 基因编码的增强子结合同源域转录因子。Ftz 与其共同因子 Ftz-F1 协同作用以激活转录。在这里，我们研究了 Ftz 和 Ftz-F1 是否优先激活特定的核心启动子基序来激活转录。我们的分析表明，与 Caudal 相似，Ftz 和 Ftz-F1 激活含有 TATA 盒突变的启动子的水平明显高于含有 DPE 突变的启动子，因此表现出对 DPE 基序的偏好。我们进一步发现，Ftz 的靶基因富含在果蝇物种中保守的一组功能下游核心启动子元件。因此，Ftz 靶基因中功能下游核心启动子元件的独特组合（Inr、Bridge 和 DPE）突出了通过核心启动子在不同发育基因调控网络转录中进行转录调控的复杂性。
