Authors

S Kirchner¹; M Van Wyngaarden¹; H Vaikkinen¹; A P Waters¹;  ¹ WTCMP University of Glasgow

Discussion

Malaria represents one of the major global threats to human health. It is caused by unicellular parasites of the Plasmodium genus, which alternate between their mosquito vector and mammalian host. The complex life cycle requires the parasite to transition through many phases each with its own gene expression profile. Within the confined nuclear space of eukaryotic cells DNA is usually wrapped around histone octamers to form so-called nucleosomes, which are further organized into densely packed chromatin. Despite its compact organisation, key molecular players of fundamental biological processes associated with developmental transitions such as transcription, DNA replication, and DNA repair require access to the genetic code. This accessibility is tightly regulated through chromatin remodelling processes, facilitating dynamic conversion of chromatin regions between an accessible and inaccessible state. We have adapted the recently developed Assay of Transposase-Accessible Chromatin using sequencing (ATAC-seq) to the extreme AT-rich genome of the rodent malaria species Plasmodium berghei. ATAC-seq is based on the integration of next-generation sequencing compatible adaptors into regions of accessible chromatin using a hyperactive transposase. By profiling accessible chromatin regions throughout the P. berghei intra-erythrocytic development cycle we uncovered general features of the regulatory chromatin landscape in malaria parasites. These include the identification of transposase accessible chromatin sites, correlation between open chromatin in promoter regions and transcription of their downstream genes, and positioning of nucleosomes along key transcriptional features. This will set the scene for an expanded study to understand the impact of the histone code on chromatin structure and accessibility. Financial support is from the European Union through a Marie Skłodowska-Curie Individual Fellowship to S.K. (SECOMAP, Ref. 657592) and funding by the Wellcome Trust to A.P.W (Ref. 083811/Z/07/Z). The authors declare no competing financial interests.