Differentiation of malaria male gametocytes is initiated by recruitment of a chromatin remodeler to male-specific cis-acting elements (RNA-Seq)

By targeting disruption of SNF2, male gametocytes lost capacity for exflagellation completely, and transcripts of male-specific genes decreased significantly, whereas female gametocytes display normal phenotype. ChIP-seq analysis showed that gSNF2 molecules were divided into two groups according to motif sequences on the genome they were recruited: those recruited to female-specific cis-acting element, TGTRNNYACA, and those recruited to a five base motif, YGTCT, that exists on the upstream of male-specific genes. Studies using a male-specific dynein promoter demonstrated that the five-base motif is a male-specific cis-acting element. ATAC-seq analysis demonstrated that the disruption of gSNF prohibits creation of a nucleosome-free region (NFR) on the promoter of male-specific target genes, and the reduction rates of NFR correlated well with those of target gene expression. These results suggests that global changes of chromatin structure by gSNF2 occur in initial step of male development. The present study also suggested that male-specific gene expression is under the control of a single kind of male-specific cis-acting element thus a single sequence-specific TF. This is a first report genome-wide changes of nucleosome positioning by a remodeling complex play a role in stage conversion of this parasite. Overall design: Plasmodium berghei transcriptomes were analyzed in gametocytes.