Abstract
Trichomonas vaginalis is an extracellular flagellated protozoan parasite that causes trichomoniasis, one of the most common non-viral sexually transmitted diseases. To survive and to maintain infection, T. vaginalis adapts to a hostile host environment by regulating gene expression. However, the mechanisms of transcriptional regulation are poorly understood for this parasite. Histone modification has a marked effect on chromatin structure and directs the recruitment of transcriptional machinery, thereby regulating essential cellular processes. In this study, we aimed to outline modes of chromatin-mediated gene regulation in T. vaginalis. Inhibition of histone deacetylase (HDAC) alters global transcriptional responses and induces hyperacetylation of histones and hypermethylation of H3K4. Analysis of the genome of T. vaginalis revealed that a number of enzymes regulate histone modification, suggesting that epigenetic mechanisms are important to controlling gene expression in this organism. Additionally, we describe the genome-wide localization of two histone H3 modifications (H3K4me3 and H3K27Ac), which we found to be positively associated with active gene expression in both steady and dynamic transcriptional states. These results provide the first direct evidence that histone modifications play an essential role in transcriptional regulation of T. vaginalis, and may help guide future epigenetic research into therapeutic intervention strategies against this parasite.
Highlights
Mechanisms, including sequence-specific DNA binding proteins and their cognate DNA regulatory elements, as well as modulation of chromatin structure[10]
To delineate the role of histone acetylation in transcriptional regulation, T. vaginalis cells were cultured in the presence or absence of apicidin, a class I/II histone deacetylases (HDACs) inhibitor[21], for 4 hours, after which gene expression profiles were compared by RNA sequencing (RNA-seq) analysis
We completed the first mapping of the epigenome of T. vaginalis and identified H3K4me[3] and H3K27Ac as global epigenetic marks for active gene expression in the steady state, as well as during dynamic transcriptional changes (Supplementary Fig. 7)
Summary
Mechanisms, including sequence-specific DNA binding proteins and their cognate DNA regulatory elements, as well as modulation of chromatin structure[10]. One study has shown that T. vaginalis uses a metazoan initiator-like element as the sole core promoter element to initiate the transcription of most of its protein-coding genes[11]. This initiator element was found to be recognized by the initiator binding protein IBP3912, which interacts with the C-terminal domain of RNA polymerase II11. Many HDAC inhibitors have been shown to increase the acetylation of core histones, resulting in altered gene expression, and are being investigated as drugs for a range of diseases, including cancers and infectious diseases[19,20]. We examined whether iron-regulated gene expression is subject to epigenetic regulation
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