RT Journal Article SR Electronic T1 Landscape and dynamics of transcription initiation in the malaria parasite Plasmodium falciparum JF bioRxiv FD Cold Spring Harbor Laboratory SP 024356 DO 10.1101/024356 A1 Sophie H. Adjalley A1 Christophe D. Chabbert A1 Bernd Klaus A1 Vicent Pelechano A1 Lars M. Steinmetz YR 2015 UL http://biorxiv.org/content/early/2015/08/10/024356.abstract AB The lack of a comprehensive map of transcription start sites (TSS) across the highly AT-rich genome of P. falciparum has hindered progress towards deciphering the molecular mechanisms that underly 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 transcriptional 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.