Toxoplasma transcription factor TgAP2XI-5 regulates the expression of genes involved in parasite virulence and host invasion

Walker, Robert, Gissor, Mathieu, Huot, Ludovic, Alayi, Tchilabalo Dilezitoko, Hot, David, Marot, Guillemette, Schaeffer-Reiss, Christine, Van Dorsselaer, Alain, Kim, Kami, and Tomavo, Stanislas (2013) Toxoplasma transcription factor TgAP2XI-5 regulates the expression of genes involved in parasite virulence and host invasion. Journal of Biological Chemistry, 288 (43). pp. 31127-31138.

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Gene regulation in apicomplexan parasites, a phylum containing important protozoan parasites such as Plasmodium and Toxoplasma, is poorly understood. The life cycle of T. gondii is complex, with multiple proliferation and differentiation steps of which tachyzoite proliferation is the most relevant to pathogenesis in humans and animals. Tachyzoites express invasion and virulence factors that are crucial for their survival and manipulation of host cell functions. The expression of those factors is tightly controlled during the tachyzoite cell cycle to permit their correct packaging in newly formed apical secretory organelles named micronemes and rhoptries in the daughter cells. However, little is known about the factors that control the expression of genes encoding the virulence factors present in these parasite-specific secretory organelles. We report that the plant-like nuclear factor TgAP2XI-5 targets more than 300 gene promoters and actively controls the transcription of these genes. Most of these target genes, including those that are essential for parasite virulence, showed a peak of expression in S and M phases of the cell cycle. Furthermore, we identified the cis-regulatory element recognized by TgAP2XI-5 and demonstrated its ability to actively drive gene transcription. Our results demonstrated that TgAP2XI-5 is a novel DNA sequence-specific transcription factor associated with promoter activation. TgAP2XI-5 may regulate gene transcription of crucial virulence factors in T. gondii.

Item ID: 29295
Item Type: Article (Research - C1)
ISSN: 1083-351X
Keywords: gene expression, gene regulation, gene transcription, infectious diseases, promoters
Funders: Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), French National Research Agency (ANR), National Institutes of Health
Projects and Grants: ANR-09-MIEN-002-01, ANR-11-LABX-0024, National Institutes of Health grant R01AI087625, National Institutes of Health grant RC4AI092801
Date Deposited: 10 Oct 2013 06:45
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060404 Epigenetics (incl Genome Methylation and Epigenomics) @ 50%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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