title: PfAP2Tel, harbouring a non-canonical DNA-binding AP2 domain, binds to Plasmodium falciparum telomeres.
abstract: The telomeres of the malaria parasite Plasmodium falciparum are essential not only for chromosome end maintenance during blood stage development in humans but also to generate genetic diversity by facilitating homologous recombination of subtelomeric, multigene virulence families such as var and rifin. However, other than the telomerase PfTERT, proteins that act at P. falciparum telomeres are poorly characterised. To isolate components that bind to telomeres, we performed oligonucleotide pulldowns and electromobility shift assays with a telomeric DNA probe and identified a non-canonical member of the ApiAP2 family of transcription factors, PfAP2Tel (encoded by PF3D7_0622900), as a component of the P. falciparum telomere-binding protein complex. PfAP2Tel is expressed throughout the intra-erythrocytic life cycle and localises to the nuclear periphery, co-localising with telomeric clusters. Furthermore, EMSAs using the recombinant protein demonstrated direct binding of PfAP2Tel to telomeric repeats in vitro, while genome-wide chromatin immunoprecipitation followed by next generation sequencing corroborated the high specificity of this protein to telomeric ends of all 14 chromosomes in vivo. Taken together, our data describe a novel function for ApiAP2 proteins at chromosome ends and open new avenues to study the molecular machinery that regulates telomere function in P. falciparum.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Miguel
authors.identifier: 0000-0001-6147-833X
authors.initials: M
authors.lastname: Sierra-Miranda
authors.affiliation: Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 2581, Institut Pasteur Paris, Paris, France.|CNRS ERL9195, Paris, France.|INSERM U1201, Paris, France.
authors.forename: Shruthi-Sridhar
authors.identifier: 0000-0002-7497-6378
authors.initials: SS
authors.lastname: Vembar
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Dulce María
authors.identifier: 0000-0002-5057-7727
authors.initials: DM
authors.lastname: Delgadillo
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Pedro A
authors.identifier: 0000-0002-0104-0771
authors.initials: PA
authors.lastname: Ávila-López
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Abril-Marcela
authors.identifier: 0000-0001-5292-115X
authors.initials: AM
authors.lastname: Herrera-Solorio
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Daniela
authors.identifier: 0000-0002-5709-4875
authors.initials: D
authors.lastname: Lozano Amado
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Miguel
authors.identifier: 0000-0002-3031-9798
authors.initials: M
authors.lastname: Vargas
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, México.
authors.forename: Rosaura
authors.identifier: 0000-0002-5275-0730
authors.initials: R
authors.lastname: Hernandez-Rivas
mesh_terms: D000940:Antigenic Variation / Q000235:genetics* / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D059014:High-Throughput Nucleotide Sequencing; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D000072417:Protein Domains / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D015342:DNA Probes; D004268:DNA-Binding Proteins; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases