title: Nuclear glycolytic enzyme enolase of Toxoplasma gondii functions as a transcriptional regulator.
abstract: Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5' untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in transcript levels of numerous gene targets. Targeted disruption of TgENO1 gene results in a decrease in brain cyst burden of chronically infected mice and in changes in transcript levels of several nuclear genes. Complementation of this knockout mutant with ectopic TgENO1-HA fully restored normal transcript levels. Our findings reveal that enolase functions extend beyond glycolytic activity and include a direct role in coordinating gene regulation in T. gondii.
authors.affiliation: Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mouveaux
authors.affiliation: Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Oria
authors.affiliation: Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Werkmeister
authors.affiliation: Laboratory of Cell Physiology, INSERM U 1003, Université Lille Nord de France, Villeneuve d'Ascq, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fox
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bzik
authors.affiliation: Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics; D051379:Mice; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism*; D014123:Toxoplasmosis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D010751:Phosphopyruvate Hydratase