PfSET2 is involved in genome organization of var gene family in Plasmodium falciparum [RNAseq]

The three-dimensional (3D) genome structure of human malaria parasite Plasmodium falciparum is highly organized and plays important roles in regulating coordinated expression patterns of specific genes such as virulence genes which are involved in antigenic variation and immune escape. However, the molecular mechanisms that control 3D genome of the parasite remain elusive. Here by analyzing genome organization in P. falciparum, we identify high-interacting regions (HIRs) with strong chromatin interactions telomeres and virulence genes loci. Specifically, HIRs are highly enriched with repressive histone marks (H3K36me3 and H3K9me3) and form the transcriptional repressive center. Deletion of PfSETvs, which controls H3K36me3 level, results in marked reduction of both intra-chromosomal and inter-chromosomal interactions for HIRs. Importantly, such chromatin reorganization coordinates with dymamic changes in epigenetic feature in HIRs and specifically activation of var genes. Our results uncover a fundamental mechanism that the epigenetic factor PfSETvs controls the 3D organization of heterochromatin in regulating the transcription activities of var genes family in P. falciparum. we generate Hi-C maps for wild-type and PfSETvs-KO samples at Ring stage in P.falciparum. Analysis of these datasets together with H3K9me3 and H3K36me3 and gene expression data allow us to uncover the changes in 3D genome with the epigenome changes and regulation of antigenic variation in the parasite.