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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
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Role of PfMYST in DNA replication in Plasmodium falciparum

Shashank Shekhar1, Krishanu Bhowmick1, Suman Kumar Dhar1

  • 1Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.

Experimental Parasitology
|October 13, 2022
PubMed

Insights

Plasmodium histone acetyltransferase PfMYST plays a key role in parasite DNA replication. This chromatin modifier binds to autonomously replicating sequences, potentially offering a target for parasite growth intervention.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Parasitology

Background:

  • Histone acetylation/deacetylation regulates eukaryotic transcription and DNA replication.
  • PfGCN5 and PfMYST are key histone acetyltransferases in Plasmodium.
  • PfMYST contains MYST, zinc finger, and chromodomains, primarily acetylating histone 4.

Purpose of the Study:

  • To investigate the role of PfMYST in Plasmodium DNA replication.
  • To characterize PfMYST isoforms and their nuclear localization.
  • To compare PfMYST and PfGCN5 binding at autonomously replicating sequences.

Main Methods:

  • Analysis of PfMYST protein isoforms (long and short).
  • Assessment of PfMYST and PfGCN5 binding to Plasmodium autonomously replicating sequences (PfARS).
  • Measurement of H4 acetylation levels at PfARS.
  • Correlation analysis with PfORC1 and parasite replication stage.

Main Results:

  • PfMYST is expressed in two isoforms (long, ~72 kDa; short, ~45 kDa), with the short isoform predominantly in the nucleus.
  • PfMYST exhibits stronger binding to PfARS compared to PfGCN5.
  • PfMYST binding correlates with increased H4 acetylation at PfARS.
  • PfMYST binding is associated with PfORC1 and the trophozoite replication stage.

Conclusions:

  • PfMYST has a potential role in Plasmodium DNA replication via chromatin modification.
  • The findings suggest PfMYST as a potential target for parasite growth intervention.
Keywords:
ARSHATHistone H4K8AcMYSTPlasmodiumReplication

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