Integration analysis of ATAC-seq and RNA-seq provides insight into the development of Plasmodium falciparum after low-temperature stress

To investigate the integration of the landscape and dynamic chromatin structure and differential expression profiling during the temperature-sensitive stages of asexual replication in the human malaria parasite Plasmodium, we combined ATAC-seq and RNA-seq to globally evaluate regions of chromatin accessibility. By analysing the two culture temperatures at the two developmental stages, we identified more than 6,300 regulatory regions, and the majority of these sites (~80%) were found within 3 kb upstream of transcripts and covered more than 4,900 transcripts. By parallel analysis of open chromatin structures during the parasite ring and trophozoite stages at physiologically relevant temperatures of 37degree and 26degree, we determined that ring stage has more differentially accessible regions (DARs), whereas no DAR was detected in trophozoite stage in response to low-temperature stress. In this study, we showed that low temperature in P. falciparum changed chromatin accessibility and activated transcription at the ring stage but not at the trophozoite stage. The impact of temperature on Plasmodium development may be influential in the ring stage, yet the underlying mechanism requires further testing. Furthermore, the DNA sequences of both stages at 37degree presented more than 442 DARs, which adequately influenced the stage-specific expression patterns of certain reporter genes. These data suggest that open chromatin structures are the main stage-specific expression of P. falciparum during blood stage development. On the basis of the association analysis of DARs identified in the promoter regions via ATAC-seq and differentially expressed genes (DEGs) from RNA-seq, certain downregulated genes exhibiting gain or loss DARs were identified. Moreover, some upregulated genes have gain or loss DARs. These findings suggest that the interaction of transcription factors with DNA sequences can modulate gene expression in P. falciparum by the change of chromatin structures.