Key result
Depletion of TbRRM1 in Trypanosoma brucei leads to decreased nascent RNA and chromatin compaction in regions distal to the main transcription start site.
Why the study?
Recent reports suggested trypanosomes could regulate RNA Pol II transcription by epigenetic mechanisms, prompting investigation into the role of TbRRM1 in transcriptional regulation of RNA Pol II-dependent genes.
This study provides experimental evidence that TbRRM1 is involved in the transcriptional regulation of RNA Pol II-dependent genes in Trypanosoma brucei by maintaining an open chromatin state.
Hypothesis-generating for TbRRM1 in trypanosome transcription; leaves open therapeutic targeting pending validation in disease models.
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.
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Bañuelos et al. (2019) studied Trypanosoma brucei. TbRRM1 depletion was evaluated on Transcriptional regulation of RNA Pol II-dependent genes. Depletion of TbRRM1 in Trypanosoma brucei leads to decreased nascent RNA and chromatin compaction in regions distal to the main transcription start site.
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