Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (IIB-UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 25 de Mayo y Francia, San Martín, Buenos Aires, Argentina.
J Eukaryot Microbiol. 2019 Sep;66(5):719-729. doi: 10.1111/jeu.12716. Epub 2019 Feb 28.
It has been long thought that RNA Polymerase (Pol) II transcriptional regulation does not operate in trypanosomes. However, recent reports have suggested that these organisms could regulate RNA Pol II transcription by epigenetic mechanisms. In this paper, we investigated the role of TbRRM1 in transcriptional regulation of RNA Pol II-dependent genes by focusing both in genes located in a particular polycistronic transcription unit (PTU) and in the monocistronic units of the SL-RNA genes. We showed that TbRRM1 is recruited throughout the PTU, with a higher presence on genes than intergenic regions. However, its depletion leads both to the decrease of nascent RNA and to chromatin compaction only of regions located distal to the main transcription start site. These findings suggest that TbRRM1 facilitates the RNA Pol II transcriptional elongation step by collaborating to maintain an open chromatin state in particular regions of the genome. Interestingly, the SL-RNA genes do not recruit TbRRM1 and, after TbRRM1 knockdown, nascent SL-RNAs accumulate while the chromatin state of these regions remains unchanged. Although it was previously suggested that TbRRM1 could regulate RNA Pol II-driven genes, we provide here the first experimental evidence which involves TbRRM1 to transcriptional regulation.
长期以来,人们一直认为 RNA 聚合酶(Pol)II 的转录调控在原生动物中不起作用。然而,最近的报道表明,这些生物体可以通过表观遗传机制来调节 RNA Pol II 的转录。在本文中,我们通过聚焦于位于特定多顺反子转录单元(PTU)中的基因和 SL-RNA 基因的单顺反子单元,研究了 TbRRM1 在 RNA Pol II 依赖性基因转录调控中的作用。我们表明,TbRRM1 募集在整个 PTU 中,在基因上的存在高于基因间区域。然而,其耗尽不仅导致新生 RNA 的减少,而且导致远离主要转录起始位点的区域的染色质紧缩。这些发现表明,TbRRM1 通过协作来维持基因组特定区域的开放染色质状态,促进 RNA Pol II 的转录延伸步骤。有趣的是,SL-RNA 基因不招募 TbRRM1,并且在 TbRRM1 敲低后,新生的 SL-RNAs 积累,而这些区域的染色质状态保持不变。虽然之前曾有人提出 TbRRM1 可以调节 RNA Pol II 驱动的基因,但我们在这里提供了第一个涉及 TbRRM1 的转录调控的实验证据。