The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.
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DOI:
10.1371/journal.pone.0045009
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Wassarman DA
Wassarman DA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Katzenberger RJ;Rach EA;Anderson AK;Ohler U;Wassarman DA

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为了研究RNA聚合酶II基因组织特异性转录的核心启动子元件的重要性,我们研究了果蝇睾丸特异性转录。生物信息学分析的核心启动子序列从190个基因,在睾丸中特异性表达,确定了一个10 bp的A/T丰富的基序,是相同的翻译控制元件(TCE)。TCE在Mst(3)CGP mRNA的5′端非翻译区起抑制翻译的作用,也在异源基因中起调节转录的作用。我们发现,在具有集中起始模式的基因中,TCE显著富集在睾丸中特异性表达的基因的核心启动子,但不富集在其他组织中特异性表达的基因的核心启动子。TCE位于核心启动子中,并且在黑腹亚组物种中是保守的,但在更远的物种中保守性急剧下降。在转基因果蝇中,含有TCE的短(300-400 bp)基因组区域指导报告基因的睾丸特异性转录。TCE的突变显着减少,但没有取消报告基因的转录,表明TCE是重要的,但不是必需的转录激活。最后,睾丸特异性TFIID(tTFIID)亚基的突变显着降低了一个子集的内源性TCE含有但不TCE缺乏基因的转录,表明tTFIID活性仅限于TCE含有的基因,但tTFIID是不是一个强制性的调节剂TCE含有的基因。因此,TCE是在睾丸中特异性表达的基因子集中的核心启动子元件。此外,TCE在短基因组区域的背景下,从核心启动子中的可变位置调节转录,并且依赖于和独立于tTFIID。这些发现为确定TCE调节睾丸特异性转录的机制和理解TCE在翻译和转录调节中的双重作用奠定了基础。
To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5′ untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300–400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the dual role of the TCE in translational and transcriptional regulation.
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发表时间: 1986-04-01
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