Prediction of the general transcription factors associated with RNA polymerase II in Plasmodium falciparum: conserved features and differences relative to other eukaryotes

Callebaut, Isabelle; Prat, Karine; Meurice, Edwige; Mornon, Jean‐Paul; Tomavo, Stanislas

doi:10.1186/1471-2164-6-100

Cited by 123 publications

(84 citation statements)

References 103 publications

(123 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As reported previously, the genes with PlasmoDB IDs PF3D7_0934100 and PF3D7_1314900 are putative orthologues of human XPD and p44, respectively, in P. falciparum (Bedez et al 2013;Callebaut et al 2005;Tuteja 2010). The multiple protein sequence alignment of XPD and p44 was done for six Plasmodium species along with human XPD.…”

Section: Sequence Analysis Of Pfxpd and Pfp44mentioning

confidence: 79%

“…Although putative orthologues of the TFIIH subunits were previously identified in P. falciparum, but to the best of our knowledge, none of them have been functionally characterized (Bedez et al 2013;Callebaut et al 2005;Tuteja 2010;Tajedin et al 2015). Therefore, we performed studies on XPD (PlasmoDB number PF3D7_0934100) and its interacting partner, p44 (PlasmoDB number PF3D7_1314900), from P. falciparum 3D7 strain which might aid in gaining further insights into the biology of the parasite.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

2015

View full text Add to dashboard Cite

XPD helicase, a TFIIH subunit, is essential for several processes including transcription, NER, cell cycle regulation, and apoptosis in eukaryotes. Another component of TFIIH, namely p44, is among the well-known interacting partners of XPD and is vital in regulating the helicase activities of latter. However, none of the above mentioned proteins have been functionally characterized in Plasmodium falciparum. Consequently, in this study, we performed detailed studies on XPD and its interacting partner, p44, from P. falciparum 3D7 strain. Accordingly, we expressed and purified recombinant PfXPD and its fragments and Pfp44 proteins and characterized the enzymatic activities of PfXPD and its fragments. The in vivo stage-specific expression and subcellular localizations of PfXPD and Pfp44 proteins were studied using the specific antibodies in the intraerythrocytic developmental stages of P. falciparum 3D7 strain. Our results suggest that PfXPD displays the characteristic ssDNA-dependent ATPase and 5'-3' DNA helicase activities. We also report the existence of two high molecular weight forms of p44 in P. falciparum 3D7 strain. Both PfXPD and Pfp44 colocalize in the nucleus and interact with each other, which suggest that they are most likely components of the same complex apparently, TFIIH. Furthermore, during trophozoite and schizont stages, both proteins exhibit a distinct cytoplasmic distribution pattern which implies that PfXPD and Pfp44 might also be involved in other functions. These studies will aid in understanding the basic biology of malaria parasite.

show abstract

Section: Sequence Analysis Of Pfxpd and Pfp44mentioning

confidence: 79%

Section: Introductionmentioning

confidence: 97%

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

2015

View full text Add to dashboard Cite

show abstract

“…However, that certain DNA motifs are recurrent in the promoters of these organisms and bind to nuclear factors [10−14] suggests that unrecognized transcription factors may exist, but are not encoded by genes with recognizable structural features. On the other hand, the RNA polymerase II machinery [7,15] and genes with motifs indicating potential chromatin remodeling and modification functions [6,16] are conserved within the Apicomplexa. Epigenetic processes have significant clinical relevance in light of studies that implicate the histone deacetylase Sir2 homolog in regulation of antigenic variation in P.…”

Section: Introductionmentioning

confidence: 99%

Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

et al. 2007

View full text Add to dashboard Cite

Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of virulence traits. Using the model organism Toxoplasma gondii, we characterized the epigenetic organization and transcription patterns of a contiguous 1% of the T. gondii genome using custom oligonucleotide microarrays. We show that methylation and acetylation of histones H3 and H4 are landmarks of active promoters in T. gondii that allow us to deduce the position and directionality of gene promoters with >95% accuracy. These histone methylation and acetylation “activation” marks are strongly associated with gene expression. We also demonstrate that the pattern of histone H3 arginine methylation distinguishes certain promoters, illustrating the complexity of the histone modification machinery in Toxoplasma. By integrating epigenetic data, gene prediction analysis, and gene expression data from the tachyzoite stage, we illustrate feasibility of creating an epigenomic map of T. gondii tachyzoite gene expression. Further, we illustrate the utility of the epigenomic map to empirically and biologically annotate the genome and show that this approach enables identification of previously unknown genes. Thus, our epigenomics approach provides novel insights into regulation of gene expression in the Apicomplexa. In addition, with its compact genome, genetic tractability, and discrete life cycle stages, T. gondii provides an important new model to study the evolutionarily conserved components of the histone code.

show abstract

“…Also in this group are the apicomplexan TAF1 homologues (94,95). Two bromodomain proteins unique to the apicomplexan species also harbor C-terminal SET methyltransferase domains (group IV) that, based on domain architecture, appear to be homologues of the mixed-lineage leukemia (MLL) family of methyltransferases; these bromodomain proteins are the only ones examined that also have multiple PHD fingers, another domain that can act as a histone PTM "reader" (96).…”

Section: Conservation Of Bromodomains In Protozoan Parasitesmentioning

confidence: 99%

Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development

Jeffers

Yang

Huang

et al. 2017

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARY Parasitic infections remain one of the most pressing global health concerns of our day, affecting billions of people and producing unsustainable economic burdens. The rise of drug-resistant parasites has created an urgent need to study their biology in hopes of uncovering new potential drug targets. It has been established that disrupting gene expression by interfering with lysine acetylation is detrimental to survival of apicomplexan (Toxoplasma gondii and Plasmodium spp.) and kinetoplastid (Leishmania spp. and Trypanosoma spp.) parasites. As “readers” of lysine acetylation, bromodomain proteins have emerged as key gene expression regulators and a promising new class of drug target. Here we review recent studies that demonstrate the essential roles played by bromodomain-containing proteins in parasite viability, invasion, and stage switching and present work showing the efficacy of bromodomain inhibitors as novel antiparasitic agents. In addition, we performed a phylogenetic analysis of bromodomain proteins in representative pathogens, some of which possess unique features that may be specific to parasite processes and useful in future drug development.

show abstract

Prediction of the general transcription factors associated with RNA polymerase II in Plasmodium falciparum: conserved features and differences relative to other eukaryotes

Cited by 123 publications

References 103 publications

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development

Contact Info

Product

Resources

About