Laboratorio de Interacciones Hospedero-Patógeno-UBM, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Nat Microbiol. 2023 Nov;8(11):2103-2114. doi: 10.1038/s41564-023-01483-y. Epub 2023 Oct 12.
Trypanosomes are eukaryotic, unicellular parasites, such as Trypanosoma brucei, which causes sleeping sickness, and Trypanosoma cruzi, which causes Chagas disease. Genomes of these parasites comprise core regions and species-specific disruptive regions that encode multigene families of surface glycoproteins. Few transcriptional regulators have been identified in these parasites, and the role of spatial organization of the genome in gene expression is unclear. Here we mapped genome-wide chromatin interactions in T. cruzi using chromosome conformation capture (Hi-C), and we show that the core and disruptive regions form three-dimensional chromatin compartments named C and D. These chromatin compartments differ in levels of DNA methylation, nucleosome positioning and chromatin interactions, affecting genome expression dynamics. Our data reveal that the trypanosome genome is organized into chromatin-folding domains and transcription is affected by the local chromatin structure. We propose a model in which epigenetic mechanisms affect gene expression in trypanosomes.
锥虫是真核单细胞寄生虫，如引起昏睡病的布氏锥虫和引起恰加斯病的克氏锥虫。这些寄生虫的基因组包括核心区域和物种特异性破坏区域，这些区域编码表面糖蛋白的多基因家族。在这些寄生虫中已经鉴定出少数转录调节剂，而基因组空间组织在基因表达中的作用尚不清楚。在这里，我们使用染色体构象捕获（Hi-C）在 T. cruzi 中绘制了全基因组染色质相互作用图谱，结果表明核心区和破坏区形成了三个称为 C 和 D 的三维染色质区室。这些染色质区室在 DNA 甲基化、核小体定位和染色质相互作用水平上存在差异，从而影响基因组表达动力学。我们的数据表明，锥虫基因组组织成染色质折叠域，转录受局部染色质结构的影响。我们提出了一个模型，即表观遗传机制影响锥虫中的基因表达。
