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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
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A Dynamic and Combinatorial Histone Code Drives Malaria Parasite Asexual and Sexual Development
Hilde von Grüning1, Mariel Coradin2, Mariel R Mendoza2
1Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa; Institute for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa.
Molecular & Cellular Proteomics : MCP
|January 20, 2022
Summary
This study reveals novel histone codes in the malaria parasite Plasmodium falciparum, uncovering stage-specific patterns and a unique histone code linked to gametocyte development and gene regulation.
Area of Science:
- Epigenetics and Parasitology
- Proteomics and Chromatin Biology
Background:
- Histone posttranslational modifications (PTMs) form
- histone codes
- that regulate gene expression through enzyme crosstalk.
Purpose of the Study:
- To comprehensively identify and quantify histone codes in Plasmodium falciparum.
- To investigate stage-specific histone modifications during asexual and sexual development.
Main Methods:
- Advanced quantitative middle-down proteomics was employed.
- Analysis of histone PTMs in proliferative asexual and transmissible gametocyte stages.
Main Results:
- A compendium of 77 histone PTMs on H3 and H3.3 was generated, with 34 newly identified in P. falciparum.
- Stage-specific combinatorial PTMs were discovered, including H3R17me2K18acK23ac in mature gametocytes.
- A gametocyte-specific SAGA-like complex involving AP2-G2 was linked to this histone code and gene regulation.
Conclusions:
- Investigating single histone PTMs may miss higher-order gene regulation in P. falciparum.
- Histone codes play a crucial role in regulating distinct proliferation and differentiation processes in the parasite.
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