Genome-wide map of H3K4me3 and H3K27Ac in the protozoan parasite Trichomonas vaginalis
Ontology highlight
ABSTRACT: In this study, we investigated genome-wide transcriptional and epigenetic responses of T. vaginalis to histone deacetylase (HDAC) inhibitors.
Project description:Trichomonas vaginalis is an extracellular flagellated protozoan responsible for trichomoniasis, one of the most prevalent non-viral sexually transmitted infections. To persist in the host, T. vaginalis employs sophisticated gene regulation mechanisms to adapt to hostile environmental conditions. Although transcriptional regulation is crucial for this adaptation, the specific molecular mechanisms remain poorly understood. Epigenetic regulation, particularly through histone modifications, has emerged as a key modulator of gene expression. Our previous study demonstrated the role of histone modifications H3K4me3 and H3K27Ac in promoting active transcription. However, the full extent of epigenetic regulation in T. vaginalis remained unclear. In this study, we extend these findings by exploring the repressive role of two additional histone H3 modifications, H3K9me3 and H3K27me3. Genome-wide analysis reveals that these modifications are negatively correlated with gene expression, impacting not only protein-coding genes but also repeat genes and transposable elements. These findings offer new insights into the dual role of histone modifications in both activating and repressing gene expression, providing a more comprehensive understanding of epigenetic regulation in T. vaginalis. This expanded knowledge could inform the development of novel therapeutic strategies targeting the epigenetic machinery of this parasite.
Project description:Trichomonas vaginalis is an extracellular flagellated protozoan responsible for trichomoniasis, one of the most prevalent non-viral sexually transmitted infections. To persist in the host, T. vaginalis employs sophisticated gene regulation mechanisms to adapt to hostile environmental conditions. Although transcriptional regulation is crucial for this adaptation, the specific molecular mechanisms remain poorly understood. Epigenetic regulation, particularly through histone modifications, has emerged as a key modulator of gene expression. Our previous study demonstrated the role of histone modifications H3K4me3 and H3K27Ac in promoting active transcription. However, the full extent of epigenetic regulation in T. vaginalis remained unclear. In this study, we extend these findings by exploring the repressive role of two additional histone H3 modifications, H3K9me3 and H3K27me3. Genome-wide analysis reveals that these modifications are negatively correlated with gene expression, impacting not only protein-coding genes but also repeat genes and transposable elements. These findings offer new insights into the dual role of histone modifications in both activating and repressing gene expression, providing a more comprehensive understanding of epigenetic regulation in T. vaginalis. This expanded knowledge could inform the development of novel therapeutic strategies targeting the epigenetic machinery of this parasite.
Project description:We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates.
Project description:Trichomonas vaginalis, a common sexually transmitted parasite that colonizes the human urogenital tract, secretes extracellular vesicles (TvEVs) that are taken up by human cells and are speculated to be taken up by parasites as well. While the crosstalk between TvEVs and human cells has led to insight into host:parasite interactions, the role of TvEVs in infection have largely been one-sided, with little known about the effect of TvEV uptake by T. vaginalis. Approximately 11% of infections are found to be co-infections of multiple T. vaginalis strains. Clinical isolates often differ in their adherence to and cytolysis of host cells, underscoring the importance of understanding the effects of TvEV uptake within the parasite population. To address this question our lab observed the effects of EV uptake by T. vaginalis on parasite gene expression. Using RNA-seq, we showed that TvEVs upregulate expression of predicted parasite membrane proteins and identified a novel adherence factor, heteropolysaccharide binding protein (HPB2).
Project description:The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves -2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.
Project description:The ATP binding cassette (ABC) proteins are a family of membrane transporters and regulatory proteins responsible for diverse and critical cellular process in all organisms. To date, there has been no attempt to investigate this class of proteins in the infectious parasite Trichomonas vaginalis. We have utilized a combination of bioinformatics, gene sequence analysis, gene expression and confocal microscopy to investigate the ABC proteins of T. vaginalis. We demonstrate that, uniquely among eukaryotes, T. vaginalis possesses no intact full-length ABC transporters and has undergone a dramatic expansion of some ABC protein sub-families. Furthermore, we provide preliminary evidence that T. vaginalis is able to read through in-frame stop codons to express ABC transporter components from gene pairs in a head-to-tail orientation. Finally, with confocal microscopy we demonstrate the expression and endoplasmic reticulum localization of a number of T. vaginalis ABC transporters.
Project description: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.