Respuela Patricia, Ferella Marcela, Rada-Iglesias Alvaro, Aslund Lena
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
J Biol Chem. 2008 Jun 6;283(23):15884-92. doi: 10.1074/jbc.M802081200. Epub 2008 Apr 9.
Trypanosomes are ancient eukaryotic parasites in which the protein-coding genes, organized in large polycistronic clusters on both strands, are transcribed from as yet unidentified promoters. In an effort to reveal transcriptional initiation sites, we examined the Trypanosoma cruzi genome for histone modification patterns shown to be linked to active genes in various organisms. Here, we show that acetylated and methylated histones were found to be enriched at strand switch regions of divergent gene arrays, not at convergent clusters or intra- and intergenic regions within clusters. The modified region showed a bimodular profile with two peaks centered over the 5'-regions of the gene pair flanking the strand switch region. This pattern, which demarcates polycistronic transcription units originating from bidirectional initiation sites, is likely to be common in kinetoplastid parasites as well as in other organisms with polycistronic transcription. In contrast, no acetylation was found at promoters of the highly expressed rRNA and spliced leader genes or satellite DNA or at tested retrotransposonal elements. These results reveal, for the first time, the presence of specific epigenetic marks in T. cruzi with potential implications for transcriptional regulation; they indicate that both histone modifications and bidirectional transcription are evolutionarily conserved.
锥虫是古老的真核寄生虫，其蛋白质编码基因以大的多顺反子簇的形式排列在两条链上，由尚未确定的启动子转录。为了揭示转录起始位点，我们在克氏锥虫基因组中研究了与各种生物体中活性基因相关的组蛋白修饰模式。在此，我们发现乙酰化和甲基化组蛋白在不同基因阵列的链转换区域富集，而不在汇聚簇或簇内及基因间区域。修饰区域呈现双峰分布，两个峰集中在链转换区域两侧基因对的5'区域上方。这种模式划定了源自双向起始位点的多顺反子转录单元，可能在动基体寄生虫以及其他有多顺反子转录的生物体中普遍存在。相比之下，在高表达的rRNA和剪接前导基因的启动子、卫星DNA或测试的反转录转座元件处未发现乙酰化。这些结果首次揭示了克氏锥虫中存在特定的表观遗传标记，对转录调控具有潜在影响；表明组蛋白修饰和双向转录在进化上都是保守的。
