3D genome organization drives gene expression in trypanosomes

Abstract

In trypanosomes, eukaryotic unicellular pathogens that cause disabling human and animal diseases, very few transcriptional regulatory elements have been described and it is largely accepted that they regulate gene expression mainly post-transcriptionally. In this regard, the role of the spatial organization of the genome on gene expression and vice versa remains practically unexplored. The genome of these parasites is partitioned into core (highly conserved syntenic) and species-specific disruptive regions (synteny disruption), containing multigene families encoding for surface glycoproteins. By mapping genome-wide chromatin interactions we demonstrate that these regions constitute 3D compartments (C and D). These chromatin compartments present significant differences in DNA methylation, nucleosome positioning and chromatin interactions, affecting genome expression dynamics. We show that the genome is organized into chromatin folding domains and transcription is dramatically determined by the local chromatin structure. Our results support a model in which epigenetic mechanisms dramatically impact gene expression in these eukaryotic pathogens.