Landscape and Dynamics of Transcription Initiation in the Malaria Parasite Plasmodium falciparum

Abstract

Summary A comprehensive map of transcription start sites (TSS) across the highly AT-rich genome of P. falciparum would aid progress towards deciphering the molecular mechanisms that underlie the timely regulation of gene expression in this malaria parasite. Using high-throughput sequencing technologies, we generated a comprehensive atlas of transcription initiation events at single nucleotide-resolution during the parasite intra-erythrocytic developmental cycle. This detailed analysis of TSS usage enabled us to define architectural features of plasmodial promoters. We demonstrate that TSS selection and strength are constrained by local nucleotide composition. Furthermore, we provide evidence for coordinate and stage-specific TSS usage from distinct sites within the same transcription unit, thereby producing transcript isoforms, a subset of which are developmentally regulated. This work offers a framework for further investigations into the interactions between genomic sequences and regulatory factors governing the complex transcriptional program of this major human pathogen.

Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae

“…mutually exclusive expression, we examined the distribution of histone modifications in the promoter region of var genes. PF3D7_1255200 belongs to the UPSB class of var genes, whose promoters are located around 50 bp upstream of the ATG41. The in silico analysis performed by Campbell et al 33.…”

“…A recent study mapped transcription start sites in P. falciparum at high resolution and revealed that 81% of the TSSs were positioned less than 1000 bp upstream of the start codon, and more than half of these are located within a distance of 500 bp or less3941. We thus used the gene ensemble available at PlasmoDB (Pf3D7 v25) for genome-wide analysis and considered the ATG ±1000 bp upstream as the putative promoter region.…”

Epigenetic Players of Chromatin Structure Regulation in Plasmodium falciparum

“…[56] But emerging reports suggested that nucleosome dynamics of ap arasite in RBC stages is not mainly mediated by AT-rich genomeo rt hrough histone variants. [59,60] This strongly suggests that the formation of chromatin structure in Plasmodium may require extra-nucleosomal positioning signals to achieve the chromatino rganization in the parasite. Studies have already shown that chromatin-based regulators play an important role in orchestrating chromatin dynamics in P. falciparum duringv ariouss tages of the life cycle.…”

“…It was proposed that these effects could be due to very high AT‐rich (81 %) in the genome that may affect the proper positioning of nucleosomes in P. falciparum . But emerging reports suggested that nucleosome dynamics of a parasite in RBC stages is not mainly mediated by AT‐rich genome or through histone variants . This strongly suggests that the formation of chromatin structure in Plasmodium may require extra‐nucleosomal positioning signals to achieve the chromatin organization in the parasite.…”

Recent advances in malaria genomics and epigenomics

“…A recent study found evidence for stage-specific transcription initiation from distinct TSSs of otherwise identical transcriptional units, giving rise to developmentally regulated mRNA isoforms [42]. While most canonical eukaryotic transcription factors are absent from the Plasmodium genome [2], the ApiAP2 family of DNA-binding proteins comprises by far the largest group of transcription factors in malaria parasites [43].…”