Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 17:10:618454.
doi: 10.3389/fcimb.2020.618454. eCollection 2020.

From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium

Thomas Hollin  1 , Karine G Le Roch  1
Affiliations
Review

From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium

Thomas Hollin et al. Front Cell Infect Microbiol. .

Abstract

Over the past decade, we have witnessed significant progresses in understanding gene regulation in Apicomplexa including the human malaria parasite, Plasmodium falciparum. This parasite possesses the ability to convert in multiple stages in various hosts, cell types, and environments. Recent findings indicate that P. falciparum is talented at using efficient and complementary molecular mechanisms to ensure a tight control of gene expression at each stage of its life cycle. Here, we review the current understanding on the contribution of the epigenome, atypical transcription factors, and chromatin organization to regulate stage conversion in P. falciparum. The adjustment of these regulatory mechanisms occurring during the progression of the life cycle will be extensively discussed.

Keywords: AP2-G; Plasmodium; chromatin; epigenetics; gene regulation; sexual commitment.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Dynamic chromatin architecture and epigenetic regulation in asexual blood stages of P. falciparum. During the IDC, drastic re-organization of the chromatin is observed to promote the transcriptional burst in trophozoite stage. The chromatin is lightly packed and enriched in active histone marks. The size of the nucleus increases as well as the number of nuclear pores. Throughout the IDC, centromeres (spheres) are clustered and located at the periphery of the nucleus while telomere regions (rectangles) form a repressive cluster on the opposite side.
Figure 2
Figure 2
Regulation of the mutually exclusive var gene expression. The subtelomeric and internal var genes are grouped in the repressive cluster and maintained in a silent state with the presence of repressive marks and the expression of specific lncRNAs. For the active var gene present at the nuclear periphery, epigenetic changes occur and require the involvement of protein modifiers.
Figure 3
Figure 3
Sexual commitment in Plasmodium falciparum. Cellular and molecular mechanisms maintain in a poised state the sexual and asexual proliferation. Epigenetic regulation and global changes of chromatin structure are fundamental for the expression of PfAP2-G and initiation of gametocytogenesis. Depending on the timing of PfAP2-G stabilization, two differentiation pathways have been identified: NCC, Next Cycle Conversion and SCC, Same Cycle Conversion.
See this image and copyright information in PMC

References

    1. Adjalley S. H., Scanfeld D., Kozlowski E., Llinás M., Fidock D. A. (2015). Genome-wide transcriptome profiling reveals functional networks involving the Plasmodium falciparum drug resistance transporters PfCRT and PfMDR1. BMC Genomics 16, 1090. 10.1186/s12864-015-2320-8 - DOI - PMC - PubMed
    1. Amit-Avraham I., Pozner G., Eshar S., Fastman Y., Kolevzon N., Yavin E., et al. (2015). Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. U. S. A. 112, E982–E991. 10.1073/pnas.1420855112 - DOI - PMC - PubMed
    1. Arnot D. E., Ronander E., Bengtsson D. C. (2011). The progression of the intra-erythrocytic cell cycle of Plasmodium falciparum and the role of the centriolar plaques in asynchronous mitotic division during schizogony. Int. J. Parasitol. 41, 71–80. 10.1016/j.ijpara.2010.07.012 - DOI - PubMed
    1. Ay F., Bunnik E. M., Varoquaux N., Bol S. M., Prudhomme J., Vert J. P., et al. (2014). Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression. Genome Res. 24, 974–988. 10.1101/gr.169417.113 - DOI - PMC - PubMed
    1. Balaji S., Madan Babu M., Iyer L. M., Aravind L. (2005). Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains. Nucleic Acids Res. 33, 3994–4006. 10.1093/nar/gki709 - DOI - PMC - PubMed

Publication types

Substances

LinkOut - more resources