Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
Department of Biology, Biochemistry and Molecular Biology Program, Trent University, Peterborough, ON, Canada.
Mol Microbiol. 2021 May;115(5):1039-1053. doi: 10.1111/mmi.14710. Epub 2021 Mar 12.
Giardia duodenalis is a parasite of great medical interest due to the number of infections it causes worldwide each year. Although research on epigenetic mechanisms in this protist has only begun recently, epigenetic regulation has already been shown to have important roles in encystation, antigenic variation, and resistance to antibiotics in Giardia. In this work, we show that a Giardia ortholog of Sir2, GdSir2.4, is involved in the silencing of rRNA expression. Our results demonstrate that GdSir2.4 localizes to the nucleolus, and its binding to the intergenic spacer region of the rDNA is associated with the deacetylation of the chromatin in this region. Given the importance of the regulation of rRNA expression to maintain adequate levels of ribosomes and genomic stability within the cells, GdSir2.4 can be considered a target to create new therapeutic agents against this parasite.
十二指肠贾第鞭毛虫是一种具有重要医学意义的寄生虫，因为它每年在全球范围内引起大量感染。尽管最近才开始研究这种原生动物的表观遗传机制，但已经表明表观遗传调控在贾第鞭毛虫的囊形成、抗原变异和对抗生素的耐药性方面发挥着重要作用。在这项工作中，我们表明，一种贾第鞭毛虫的 Sir2 同源物，GdSir2.4，参与了 rRNA 表达的沉默。我们的结果表明，GdSir2.4 定位于核仁，它与 rDNA 基因间区的结合与该区域染色质的去乙酰化有关。鉴于调节 rRNA 表达对于维持细胞内核糖体和基因组稳定性的重要性，GdSir2.4 可以被认为是针对这种寄生虫的新型治疗药物的靶点。
