Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite.
The molecular mechanisms underlying transcriptional regulation in apicomplexan parasites remain poorly understood. Recently, the Apicomplexan AP2 (ApiAP2) family of DNA binding proteins was identified as a major class of transcriptional regulators that are found across all Apicomplexa. To gain insight into the regulatory role of these proteins in the malaria parasite, we have comprehensively surveyed the DNA-binding specificities of all 27 members of the ApiAP2 protein family from Plasmodium falciparum revealing unique binding preferences for the majority of these DNA binding proteins. In addition to high affinity primary motif interactions, we also observe interactions with secondary motifs. The ability of a number of ApiAP2 proteins to bind multiple, distinct motifs significantly increases the potential complexity of the transcriptional regulatory networks governed by the ApiAP2 family. Using these newly identified sequence motifs, we infer the trans-factors associated with previously reported plasmodial cis-elements and provide evidence that ApiAP2 proteins modulate key regulatory decisions at all stages of parasite development. Our results offer a detailed view of ApiAP2 DNA binding specificity and take the first step toward inferring comprehensive gene regulatory networks for P. falciparum.
Department of Molecular Biology & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
Tracey L
TL
Campbell
Erandi K
EK
De Silva
Kellen L
KL
Olszewski
Olivier
O
Elemento
Manuel
M
Llinás
D000818:Animals; D016782:Apicomplexa / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology; D009033:Culicidae; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D005544:Forecasting; D005786:Gene Expression Regulation; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology; D005810:Multigene Family / Q000502:physiology; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C083115:activator protein-2 binding element; D004247:DNA