title: Toxoplasma transcription factor TgAP2XI-5 regulates the expression of genes involved in parasite virulence and host invasion.
abstract: Gene regulation in apicomplexan parasites, a phylum containing important protozoan parasites such as Plasmodium and Toxoplasma, is poorly understood. The life cycle of Toxoplasma 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 the 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.
authors.affiliation: From the Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM 1019, Université Lille Nord de France, Institut Pasteur de Lille, 59 000 Lille, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Walker
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gissot
authors.forename: Ludovic
authors.initials: L
authors.lastname: Huot
authors.forename: Tchilabalo Dilezitoko
authors.initials: TD
authors.lastname: Alayi
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.forename: Guillemette
authors.initials: G
authors.lastname: Marot
authors.forename: Christine
authors.initials: C
authors.lastname: Schaeffer-Reiss
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Kami
authors.initials: K
authors.lastname: Kim
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D017125:Genes, Protozoan / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D014157:Transcription Factors
keywords: Gene Expression; Gene Regulation; Gene Transcription; Infectious Diseases; Promoters
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