scholarly journals Activity of epigenetic inhibitors against Plasmodium falciparum asexual and sexual blood stages

2019 ◽  
Author(s):  
Leen Vanheer ◽  
Björn F.C. Kafsack
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Epigenetic Regulation ◽  
Malaria Parasite ◽  
Regulation Of Gene Expression ◽  
Life Stages ◽  
Multi Stage ◽  
Promising Target ◽  
Parasite Survival ◽  
Epigenetic Processes

AbstractRegulation of gene expression by epigenetic processes is critical for malaria parasite survival in multiple life stages. To evaluate the suitability of targeting these pathways we screened 350 epigenetic inhibitors against asexual blood stages and gametocytes of P. falciparum. We observed ≥90% inhibition at 10 µM for 28% of compounds, of which a third retained ≥90% inhibition at 1 µM. These results suggest epigenetic regulation as a promising target for the development of new multi-stage anti-malarials.

scholarly journals Activity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood Stages

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Leen N. Vanheer ◽  
Hao Zhang ◽  
Gang Lin ◽  
Björn F. C. Kafsack
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Epigenetic Regulation ◽  
Malaria Parasite ◽  
Regulation Of Gene Expression ◽  
Life Stages ◽  
Content Type ◽  
Promising Target ◽  
Parasite Survival ◽  
Multiple Stages

ABSTRACT Earlier genetic and inhibitor studies showed that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new antimalarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum. We observed ≥90% inhibition at 10 μM for 28% of compounds against asexual blood stages and early gametocytes, of which a third retained ≥90% inhibition at 1 μM.

Epigenetic control of development and expression of quantitative traits

2011 ◽  
Vol 23 (1) ◽  
pp. 64 ◽  
Author(s):  
Hélène Jammes ◽  
Claudine Junien ◽  
Pascale Chavatte-Palmer
Keyword(s):  
Gene Expression ◽  
Embryo Development ◽  
Epigenetic Regulation ◽  
Quantitative Traits ◽  
Regulation Of Gene Expression ◽  
Biological Processes ◽  
Epigenetic Control ◽  
Complex Interactions ◽  
Epigenetic Processes

In recent years, it has become increasingly clear that epigenetic regulation of gene expression is critical during embryo development and subsequently during pre- and post-natal life. The phenotype of an individual is the result of complex interactions between genotype and current, past and ancestral environment leading to a lifelong remodelling of its epigenome. Practically, if the genome was compared with the hardware in a computer, the epigenome would be the software that directs the computer’s operation. This review points to the importance of epigenetic processes for genome function in various biological processes, such as embryo development and the expression of quantitative traits.

scholarly journals G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum

2021 ◽  
Author(s):  
Franck Dumetz ◽  
Eugene Yui-Ching Chow ◽  
Lynne M. Harris ◽  
Mubarak I. Umar ◽  
Anders Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Regulation Of Gene Expression ◽  
Low Complexity ◽  
Telomere Maintenance ◽  
Translation Efficiency ◽  
G Quadruplex

ABSTRACTG-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.

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