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Role of PfGCN5 in nutrient sensing and transcriptional regulation in Plasmodium falciparum

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Abstract

Malaria is a deadly, infectious disease caused by the parasite Plasmodium, leading to millions of deaths worldwide. Plasmodium requires a coordinated pattern of sequential gene expression for surviving in both invertebrate and vertebrate host environments. As parasites largely depend on host resources, they also develop efficient mechanisms to sense and adapt to variable nutrient conditions in the environment and modulate their virulence. Earlier we have shown that PfGCN5, a histone acetyltransferase, binds to the stress-responsive and virulence-related genes in a poised state and regulates their expression under temperature and artemisinin treatment conditions in P. falciparum. In this study, we show upregulation of PfGCN5 upon nutrient stress condition. With the help of chromatin immunoprecipitation coupled high-throughput sequencing (ChIP-seq) and transcriptomic (RNA-sequencing) analyses, we show that PfGCN5 is associated with the genes that are important for the maintenance of parasite cellular homeostasis upon nutrient stress condition. Furthermore, we identified various metabolic enzymes as interacting partners of PfGCN5 by immunoprecipitation coupled with mass spectroscopy, possibly acting as a sensor of nutrient conditions in the environment. We also demonstrated that PfGCN5 interacts and acetylates PfGAPDH in vitro. Collectively, our data provides important insights into transcriptional deregulation upon nutrient stress condition and elucidate the role of PfGCN5 during nutrient stress condition.

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Acknowledgements

This work was supported by Genome Engineering Technologies program (BT/PR25858/GET/119/169/2017) of the Department of Biotechnology, India, to KK. MR is supported by the DBT-SRF fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. These authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411 008, India

    Mukul Rawat, Rashim Malhotra, Sharvani Shintre, Samarendra Pani & Krishanpal Karmodiya

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  1. Mukul Rawat
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  2. Rashim Malhotra
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  3. Sharvani Shintre
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  4. Samarendra Pani
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  5. Krishanpal Karmodiya
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Corresponding author

Correspondence to Krishanpal Karmodiya.

Additional information

This article is part of the Topical Collection: Chromatin Biology and Epigenetics.

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Supplementary Figure 1.

Venn diagram showing number of genes bound by PfGCN5 during control and nutrient stress conditions. Genes associated with antigenic variation and immune response were found to be targets of PfGCN5 under both control and nutrient stress conditions. PfGCN5 was bound to metabolic genes exclusively during nutrient stress condition. (DOCX 179 kb)

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Rawat, M., Malhotra, R., Shintre, S. et al. Role of PfGCN5 in nutrient sensing and transcriptional regulation in Plasmodium falciparum. J Biosci 45, 11 (2020). https://doi.org/10.1007/s12038-019-9981-4

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  • DOI: https://doi.org/10.1007/s12038-019-9981-4

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