title: Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor.
abstract: Stage-specific transcription is a fundamental biological process in the life cycle of the Plasmodium parasite. Proteins containing the AP2 DNA-binding domain are responsible for stage-specific transcriptional regulation and belong to the only known family of transcription factors in Plasmodium parasites. Comprehensive identification of their target genes will advance our understanding of the molecular basis of stage-specific transcriptional regulation and stage-specific parasite development. AP2-O is an AP2 family transcription factor that is expressed in the mosquito midgut-invading stage, called the ookinete, and is essential for normal morphogenesis of this stage. In this study, we identified the genome-wide target genes of AP2-O by chromatin immunoprecipitation-sequencing and elucidate how this AP2 family transcription factor contributes to the formation of this motile stage. The analysis revealed that AP2-O binds specifically to the upstream genomic regions of more than 500 genes, suggesting that approximately 10% of the parasite genome is directly regulated by AP2-O. These genes are involved in distinct biological processes such as morphogenesis, locomotion, midgut penetration, protection against mosquito immunity and preparation for subsequent oocyst development. This direct and global regulation by AP2-O provides a model for gene regulation in Plasmodium parasites and may explain how these parasites manage to control their complex life cycle using a small number of sequence-specific AP2 transcription factors.
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Kaneko
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Shiroh
authors.initials: S
authors.lastname: Iwanaga
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Core-Lab, Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005260:Female; D005786:Gene Expression Regulation; D018503:Genome, Protozoan; D059014:High-Throughput Nucleotide Sequencing; D008018:Life Cycle Stages; D008288:Malaria / Q000235:genetics* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D033661:Oocysts / Q000254:growth & development / Q000378:metabolism / Q000469:parasitology; D010962:Plasmodium berghei / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D016053:RNA, Protozoan; D017386:Sequence Homology, Amino Acid; D050656:Transcription Factor AP-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D016053:RNA, Protozoan; D050656:Transcription Factor AP-2