“Comprehensive Analysis of Nascent Transcriptome Reveals Diverse Transcriptional Profiles Across the Trypanosoma cruzi Genome Underlining the Regulatory Role of Genome Organization, Chromatin Status, and Cis-Acting Elements”
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Trypanosomatids are eukaryotic parasites exhibiting polycistronic transcription and trans-splicing. Post-transcriptional mechanisms are acknowledged as pivotal in gene expression regulation of their protein-coding genes. To comprehensively investigate the impact of transcription on gene expression in Trypanosoma cruzi and the association with the epigenetic landscape, we conducted a genome-wide nascent transcriptomic analysis. Our findings reveal significant asymmetrical transcriptional abundance across the genome, notably between polycistronic transcription units (PTUs) enriched in conserved genes (core PTUs) and those containing virulence genes (disruptive PTUs). We found that trypanosomes exploit linear genome organization to regulate transcription abundance by embedding virulence genes into highly transcribed core-enriched PTUs, by positioning PTUs near non-coding regions of small non-coding RNAs (e.g., tRNAs, snoRNAs), and by placing core CDSs in PTUs of various sizes. Additionally, we found correlations between open chromatin status and nascent transcript levels, both globally and particularly at transcription starting regions (divergent strand switch regions - dSSRs), indicating a crucial role for chromatin architecture in transcriptional regulation. While both core and disruptive dSSRs exhibit similar levels of some epigenetic marks (H2B.V deposition and 5mC), disruptive dSSRs display significantly higher 5hmC content and nucleosome occupancy compared to core dSSRs. Furthermore, we identified distinct conserved motifs within dSSRs of core and disruptive PTUs. These findings challenge the notion of constitutive and uniform transcription in T. cruzi , underscoring the paramount importance of linear genome organization, cis-acting motifs, and chromatin landscape in transcriptional regulation.
