The essential transcriptional regulator HDP1 drives expansion of the inner membrane complex during early sexual differentiation of malaria parasites

Morillo, Riward Campelo; Tong, Xinran; Xie, Wei; Abel, Steven; Orchard, Lindsey M.; Daher, Wassim; Patel, Dinshaw J.; Llinás, Manuel; Roch, Karine G. Le; Kafsack, Björn F.C.

doi:10.1101/2020.10.26.352583

Cited by 4 publications

(2 citation statements)

References 86 publications

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“…RNA-seq methodology was adapted from previous articles with modifications ( 82 , 83 ). On day 15 of gametocyte development, stage V gametocytes were harvested using saponin lysis.…”

Section: Methodsmentioning

confidence: 99%

Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector

Kumar

Baranwal

Haile

et al. 2022

mBio

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“…RNA-seq methodology was adapted from previous articles with modifications ( 82 , 83 ). On day 15 of gametocyte development, stage V gametocytes were harvested using saponin lysis.…”

Section: Methodsmentioning

confidence: 99%

Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector

Kumar

Baranwal

Haile

et al. 2022

mBio

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“…Furthermore, the homeodomain protein 1 (HDP1) was found to be an essential regulator of gene expression during the sexual differentiation of Plasmodium. HDP1 binds DNA during Plasmodium development and is tightly associated with chromatin in early gametocytes [107].…”

Section: Order Haemosporidamentioning

confidence: 99%

Sexual Development in Non-Human Parasitic Apicomplexa: Just Biology or Targets for Control?

Cruz‐Bustos

Feix

Ruttkowski

et al. 2021

Animals

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The phylum Apicomplexa is a major group of protozoan parasites including gregarines, coccidia, haemogregarines, haemosporidia and piroplasms, with more than 6000 named species. Three of these subgroups, the coccidia, hemosporidia, and piroplasms, contain parasites that cause important diseases of humans and animals worldwide. All of them have complex life cycles involving a switch between asexual and sexual reproduction, which is key to their development. Fertilization (i.e., fusion of female and male cells) results in the formation of a zygote that undergoes meiosis, forming a new generation of asexual stages. In eukaryotes, sexual reproduction is the predominant mode of recombination and segregation of DNA. Sex is well documented in many protist groups, and together with meiosis, is frequently linked with transmission to new hosts. Apicomplexan sexual stages constitute a bottleneck in the life cycle of these parasites, as they are obligatory for the development of new transmissible stages. Consequently, the sexual stages represent attractive targets for vaccination. Detailed understanding of apicomplexan sexual biology will pave the way for the design and implementation of effective transmission-blocking strategies for parasite control. This article reviews the current knowledge on the sexual development of Apicomplexa and the progress in transmission-blocking vaccines for their control, their advantages and limitations and outstanding questions for the future.

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DNA sequence context and the chromatin landscape differentiate sequence-specific transcription factor binding in the human malaria parasite,Plasmodium falciparum

Bonnell

Zhang

Brown

et al. 2023

Preprint

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Development of the human malaria parasite,Plasmodium falciparum, is regulated by a limited number of sequence-specific transcription factors (TFs). However, the mechanisms by which these TFs recognize genome-wide binding sites is still largely unknown. To address TF specificity, we investigated the binding of two TF subsets that either bind CACACA or GTGCAC DNA sequence motifs and further characterized PfAP2-G and PfAP2-EXP which bind unique DNA motifs (GTAC and TGCATGCA). We interrogated the impact of DNA sequence and chromatin context onP. falciparumTF binding by integrating high-throughputin vitroandin vivobinding assays, DNA shape predictions, epigenetic post-translational modifications, and chromatin accessibility. We determined that DNA sequence context minimally impacts binding site selection for CACACA-binding TFs, while chromatin accessibility, epigenetic patterns, co-factor recruitment, and dimerization contribute to differential binding. In contrast, GTGCAC-binding TFs prefer different DNA sequence context in addition to chromatin dynamics. Finally, we find that TFs that preferentially bind divergent DNA motifs may bind overlapping genomic regionsin vivodue to low-affinity binding to other sequence motifs. Our results demonstrate that TF binding site selection relies on a combination of DNA sequence and chromatin features, thereby contributing to the complexity ofP. falciparumgene regulatory mechanisms.

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The essential transcriptional regulator HDP1 drives expansion of the inner membrane complex during early sexual differentiation of malaria parasites

Cited by 4 publications

References 86 publications

Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector

Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector

Sexual Development in Non-Human Parasitic Apicomplexa: Just Biology or Targets for Control?

DNA sequence context and the chromatin landscape differentiate sequence-specific transcription factor binding in the human malaria parasite,Plasmodium falciparum

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