Smircich Pablo, El-Sayed Najib M, Garat Beatriz
Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Republica, 11400, Montevideo, Uruguay.
Departamento de Genética, Facultad de Medicina, Universidad de la Republica, 11800, Montevideo, Uruguay.
BMC Res Notes. 2017 Nov 9;10(1):585. doi: 10.1186/s13104-017-2908-y.
Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed. In order to study whether this feature is conserved in trypanosomatids, we undertook a genome wide search for intrinsic DNA curvature in T. cruzi and T. brucei.
Using a region integrated intrinsic curvature (RIIC) scoring that we previously developed, a non-random distribution of sequence-dependent curvature was observed. High RIIC scores were found to be significantly correlated with transcription start sites in T. cruzi, which have been mapped in divergent switch regions, whereas in T. brucei, the high RIIC scores correlated with sites that have been involved not only in RNA polymerase II initiation but also in termination. In addition, we observed regions with high RIIC score presenting in-phase tracts of Adenines, in the subtelomeric regions of the T. brucei chromosomes that harbor the variable surface glycoproteins genes.
In both T. cruzi and T. brucei genomes, a link between DNA conformational signals and gene expression was found. High sequence dependent curvature is associated with transcriptional regulation regions. High intrinsic curvature also occurs at the T. brucei chromosome subtelomeric regions where the recombination processes involved in the evasion of the immune host system take place. These findings underscore the relevance of indirect DNA readout in these ancient eukaryotes.
克氏锥虫和布氏锥虫是引起恰加斯病和非洲昏睡病的原生动物寄生虫，具有独特的细胞和分子生物学特征。值得注意的是，迄今为止尚未发现驱动蛋白质编码基因转录的RNA聚合酶II启动子的典型信号。DNA的二级结构长期以来一直被认为是生物过程中的一种信号，最近有人提出它参与利什曼原虫的转录起始。为了研究这一特征在锥虫中是否保守，我们对克氏锥虫和布氏锥虫的全基因组进行了内在DNA曲率搜索。
使用我们之前开发的区域整合内在曲率（RIIC）评分，观察到序列依赖性曲率的非随机分布。在克氏锥虫中，高RIIC评分与转录起始位点显著相关，这些位点已被定位在不同的转换区域，而在布氏锥虫中，高RIIC评分与不仅参与RNA聚合酶II起始而且参与终止的位点相关。此外，我们在布氏锥虫染色体的亚端粒区域观察到高RIIC评分区域，该区域含有可变表面糖蛋白基因，存在腺嘌呤的同相序列。
在克氏锥虫和布氏锥虫基因组中，均发现了DNA构象信号与基因表达之间的联系。高序列依赖性曲率与转录调控区域相关。高内在曲率也出现在布氏锥虫染色体亚端粒区域，该区域发生了逃避免疫宿主系统的重组过程。这些发现强调了间接DNA读出在这些古老真核生物中的相关性。
