Prat Agustina, Muñoz Daniela, Lizarraga Ayelen, Seifert-Gorzycki Julieta, Sanchez-Vazquez Estefania, Johnson Patrica, Mazzulla Pablo Hernan Strobl, de Miguel Natalia
Instituto Tecnológico Chascomús (INTECH), CONICET-UNSAM.
University of California, Los Angeles.
Res Sq. 2024 Dec 16:rs.3.rs-5455511. doi: 10.21203/rs.3.rs-5455511/v1.
, the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infection's outcome varies greatly depending on different factors that include variation in human immune responses, the vaginal microbiome, and the inherent virulence of the strain. Although the pathogenicity of the different strains depends, at least partially, on differential gene expression of virulence genes; the regulatory mechanisms governing this transcriptional control remain incompletely understood. While many studies have reported a positive correlation between gene expression and chromatin accessibility in other cells, this relationship has not been analyzed in . To address these questions, we selected two contrasting strains based on their interactions with host cells: B7268 strain, a highly adherent one and resistant to metronidazole, and NYH209 strain, a poorly adherent one and sensitive to metronidazole. Next, we combined the assay for transposase-accessible chromatin using sequencing (ATAC-seq) with RNA sequencing (RNA-seq), to delve into the relationship between chromatin accessibility and gene expression in these distinct strains. Our findings demonstrate a correlation between chromatin accessibility and gene expression across both strains. Moreover, we found that chromatin accessibility plays a pivotal role in modulating mRNA expression levels of several established genes linked to parasite pathogenesis and drug resistance. We also identified several open chromatin peaks residing at intergenic regions, revealing possible distal regulatory elements that may control gene expression. These results highlight the importance of chromatin accessibility in modulating gene expression in the parasite , with possible consequences in pathogenesis and/or drug treatment.
是最常见的非病毒性性传播寄生虫,每年导致超过2.7亿例感染。感染的结果因多种因素而有很大差异,这些因素包括人类免疫反应的差异、阴道微生物群以及菌株的固有毒力。虽然不同菌株的致病性至少部分取决于毒力基因的差异基因表达,但控制这种转录调控的机制仍未完全了解。虽然许多研究报告了其他细胞中基因表达与染色质可及性之间的正相关关系,但这种关系在中尚未得到分析。为了解决这些问题,我们根据它们与宿主细胞的相互作用选择了两种对比鲜明的菌株:B7268菌株,一种高度粘附且对甲硝唑耐药的菌株,以及NYH209菌株,一种粘附性差且对甲硝唑敏感的菌株。接下来,我们将转座酶可及染色质测序分析(ATAC-seq)与RNA测序(RNA-seq)相结合,以深入研究这些不同菌株中染色质可及性与基因表达之间的关系。我们的研究结果表明,两种菌株的染色质可及性与基因表达之间存在相关性。此外,我们发现染色质可及性在调节与寄生虫发病机制和耐药性相关的几个已确定基因的mRNA表达水平方面起着关键作用。我们还确定了位于基因间区域的几个开放染色质峰,揭示了可能控制基因表达的远端调控元件。这些结果突出了染色质可及性在调节寄生虫基因表达中的重要性,可能对发病机制和/或药物治疗产生影响。