Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation
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Date
Authors
Van Biljon, Riette Andele
Van Wyk, Roelof Daniel Jacobus
Painter, Heather J.
Orchard, Lindsey
Reader, Janette
Niemand, Jandeli
Llinas, Manuel
Birkholtz, Lyn-Marie
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
BACKGROUND : Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis.
RESULTS : The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors.
CONCLUSIONS : The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.
Description
Additional File 1: Table S1 Total microarray data with GO enrichment pertaining to Fig. 1 & 2
Additional File 2. Correlation of microarray time points and gametocyte markers pertaining to Fig. 1
Additional File 3. Cross-dataset comparison and functional enrichment pertaining to Figs. 2-5
Additional file 4: Fig. S1. qPCR validation of select gametocyte genes. Fig. S2. Transcript abundance of ApiAP2 transcription factors during P. falciparum gametocyte development. Fig. S3. Transcript abundance of ap2-g and downstream genes (identified in Josling et al. 2019)
Additional File 2. Correlation of microarray time points and gametocyte markers pertaining to Fig. 1
Additional File 3. Cross-dataset comparison and functional enrichment pertaining to Figs. 2-5
Additional file 4: Fig. S1. qPCR validation of select gametocyte genes. Fig. S2. Transcript abundance of ApiAP2 transcription factors during P. falciparum gametocyte development. Fig. S3. Transcript abundance of ap2-g and downstream genes (identified in Josling et al. 2019)
Keywords
Malaria, Plasmodium, Gametocyte, Gametocytogenesis, Transcriptome, Gene expression regulation, Differentiation, Sexual development
Sustainable Development Goals
Citation
Van Biljon, R., Van Wyk, R., Painter, H.J. et al. Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation. BMC Genomics 20, 920 (2019). https://doi.org/10.1186/s12864-019-6322-9.