Genomic analysis of sequence-dependent DNA curvature in Leishmania.

Genomic analysis of sequence-dependent DNA curvature in Leishmania.
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DOI:
10.1371/journal.pone.0063068
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Garat B
Garat B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Smircich P;Forteza D;El-Sayed NM;Garat B

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硕大利什曼原虫是一种具有重要医学意义的鞭毛原生动物寄生虫。与锥虫科的其他成员一样,它具有独特的基因表达机制,如定向基因簇的组成型多顺反子转录、基因扩增、mRNA反式剪接和线粒体转录本的广泛编辑。大多数这些过程背后的分子信号仍在调查中。为了研究DNA二级结构信号在基因表达中的作用,我们对DNA固有曲率进行了全基因组的计算机分析。洛杉矶与原核生物和真核生物相比,主要基因组显示出较低频率的高内在曲率区域以及染色体间和染色体内的分布异质性。使用一种新的方法,旨在检测区域整合的内在曲率(RIIC),高DNA曲率被发现与转录起始相关的区域。这些包括定向基因簇之间的发散链转换区域和与活性转录起始标记物(如乙酰化H3组蛋白、TRF4和SNAP 50)相关的区域。这些发现表明,DNA曲率在利什曼原虫的转录起始中的作用,支持DNA二级结构信号的相关性。
Leishmania major is a flagellated protozoan parasite of medical importance. Like other members of the Trypanosomatidae family, it possesses unique mechanisms of gene expression such as constitutive polycistronic transcription of directional gene clusters, gene amplification, mRNA trans-splicing, and extensive editing of mitochondrial transcripts. The molecular signals underlying most of these processes remain under investigation. In order to investigate the role of DNA secondary structure signals in gene expression, we carried out a genome-wide in silico analysis of the intrinsic DNA curvature. The L. major genome revealed a lower frequency of high intrinsic curvature regions as well as inter- and intra- chromosomal distribution heterogeneity, when compared to prokaryotic and eukaryotic organisms. Using a novel method aimed at detecting region-integrated intrinsic curvature (RIIC), high DNA curvature was found to be associated with regions implicated in transcription initiation. Those include divergent strand-switch regions between directional gene clusters and regions linked to markers of active transcription initiation such as acetylated H3 histone, TRF4 and SNAP50. These findings suggest a role for DNA curvature in transcription initiation in Leishmania supporting the relevance of DNA secondary structures signals.
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