Epigenetic editing by CRISPR/dCas9 in .

Genetic manipulation remains a major obstacle for understanding the functional genomics of the deadliest malaria parasite Although the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9) system has been successfully applied to introduce permanent changes in the parasite genome, its use is still limited. Here we show that fusing different epigenetic effector domains to a Cas9 null mutant efficiently and specifically reprograms the expression of target genes in By precisely writing and erasing histone acetylation at the transcription start site regions of the invasion-related genes () and (), respectively, we achieved significant activation of and repression of , leading to the switch of the parasite invasion pathways into human erythrocytes. By using the epigenetic knockdown system, we have also characterized the effects of , previously identified as an essential gene, on expression of mainly trophozoite- and schizont-specific genes, and therefore regulation of the growth of the mature forms of This epigenetic CRISPR/dCas9 system provides a powerful approach for regulating gene expression at the transcriptional level in .