PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

Abstract

Plasmodium falciparum undergoes a series of asexual replications in human erythrocytes after infection, which are effective targets for combatting malaria. Here, we report roles of an ApiAP2 transcription factor PfAP2-EXP2 (PF3D7_0611200) in the intraerythrocytic developmental cycle of P. falciparum. PfAP2-EXP2 conditional knockdown resulted in an asexual growth defect but without an appreciable effect on parasite morphology. Further ChIP-seq analysis revealed that PfAP2-EXP2 targeted genes related to virulence and interaction between erythrocytes and parasites. Especially, PfAP2-EXP2 regulation of euchromatic genes does not depend on recognizing specific DNA sequences, while a CCCTAAACCC motif is found in its heterochromatic binding sites. Combined with transcriptome profiling, we suggest that PfAP2-EXP2 is participated in the intraerythrocytic development by affecting the expression of genes related to cell remodeling at the schizont stage. In summary, this study explores an ApiAP2 member plays an important role for the P. falciparum blood-stage replication, which suggests a new perspective for malaria elimination.

A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin

“…Using immunoaffinity-based purification, we identified a number of nuclear proteins that interact with PfMORC. More specifically, PfMORC was associated with PfAP2-G5, which is essential for gametocytogenesis (Shang et al 2021 ), PfAP2-I, which is required for the expression of many invasion-related genes (Santos et al 2017 ), and with other ApiAP2 TFs of unknown function (PfAP2-O5, PF3D7_1107800, PF3D7_0613800, PF3D7_0420300, and PF3D7_1239200). The identification of PfISW1 and PfCHD1 in association with PfMORC strengthens the link between PfMORC and chromatin remodeling.…”

APlasmodium falciparumMORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin

“…We identified a number of nuclear proteins that interact with Pf MORC using immunoaffinity-based purification. More specifically, Pf MORC was associated with Pf AP2-G5, which is essential for gametocytogenesis (Shang et al 2021), Pf AP2-I, which is required for the expression of many invasion-related genes (Santos et al 2017), and with other ApiAP2 TFs of unknown function during the asexual blood stage of development ( Pf AP2-O5, PF3D7_1107800, PF3D7_0613800, PF3D7_0420300, and PF3D7_1239200). The identification of Pf ISW1 and Pf CHD1 in association with Pf MORC strengthens the link between Pf MORC and a role in chromatin remodeling.…”

Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites

“…Although the majority of the ApiAP2 family TFs are associated with developmental-stage transitions, some of them seem to be required for supplementary mechanisms whose biological functions remain elusive. AP2-exp and AP2-exp2 mutants showed upregulation of antigenic variant genes (rifin, stevor, and Pfmc-2TM) and reduction of genes involved in cell remodeling, respectively (79,109). Different AP2 TFs are also associated with heterochromatin (108), such as AP2-HC (23), while AP2Tel and PfSIP2 were found to be enriched in subtelomeric regions (38,112).…”