Specific DNA-binding by Apicomplexan AP2 transcription factors

被引:183
作者
De Silva, Erandi K. [1 ,2 ]
Gehrke, Andrew R. [3 ]
Olszewski, Kellen [1 ,2 ]
Leon, Ilsa [1 ,2 ]
Chahal, Jasdave S. [1 ,2 ]
Bulyk, Martha L. [3 ,4 ,5 ]
Llinas, Manuel [1 ,2 ]
机构
[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
[2] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA
[3] Harvard Univ, Sch Med, Dept Med, Div Genet, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Boston, MA 02115 USA
关键词
gene expression; malaria; Plasmodium; protein-DNA interaction; protein-binding microarray;
D O I
10.1073/pnas.0801993105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Malaria remains one of the most prevalent infectious diseases worldwide, affecting more than half a billion people annually. Despite many years of research, the mechanisms underlying transcriptional regulation in the malaria-causing Plasmodium spp., and in Apicomplexan parasites generally, remain poorly understood. In Plasmodium, few regulatory elements sufficient to drive gene expression have been characterized, and their cognate DNA-binding proteins remain unknown. This study characterizes the DNA-binding specificities of two members of the recently identified Apicomplexan AP2 (ApiAP2) family of putative transcriptional regulators from Plasmodium falciparum. The ApiAP2 proteins contain AP2 domains homologous to the well characterized plant AP2 family of transcriptional regulators, which play key roles in development and environmental stress response pathways. We assayed ApiAP2 protein-DNA interactions using protein-binding microarrays and combined these results with computational predictions of coexpressed target genes to couple these putative trans factors to corresponding cis-regulatory motifs in Plasmodium. Furthermore, we show that protein DNA sequence specificity is conserved in orthologous proteins between phylogenetically distant Apicomplexan species. The identification of the DNA-binding specificities for ApiAP2 proteins lays the foundation for the exploration of their role as transcriptional regulators during all stages of parasite development. Because of their origin in the plant lineage, ApiAP2 proteins have no homologues in the human host and may prove to be ideal antimalarial targets.
引用
收藏
页码:8393 / 8398
页数:6
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