Soumya Shraddhya Paul, Amity University, Noida
The SAGA complex, which includes the histone acetyltransferase GCN5 and serves as a general transcription co-activator in global gene regulation, is evolutionarily conserved from yeast to humans. In a study conducted by Jun Miao along with other researchers, Plasmodium falciparum has a divergent GCN5 complex that includes two plant homeodomain (PHD) proteins (PfPHD1 and PfPHD2) and a plant apetela2 (AP2)-domain transcription factor (PfAP2-LT). All critical cellular activities, including transcription, DNA replication, and repair, are influenced by the packaging of eukaryotic genomes with nucleosomes into chromatin. Post-translational modifications (PTMs) of nucleosomal histones, which can change DNA accessibility and recruit certain PTM readers and other effector proteins, are a crucial mechanism for controlling chromatin shape.
Plasmodium and its related transcription factors
Plasmodium falciparum, the human malaria parasite, killed approximately half a million people in 2019. Its complex lifetime, which includes a vertebrate host and a mosquito vector, necessitates precise transcription control to deal with the extensive developmental program and environmental alterations that occur throughout host transitions. Even for the conserved TFs, data suggests that the malaria parasite has unique transcriptional regulatory characteristics that differ from other eukaryotes. Although the Plasmodium genome encodes the majority of the general transcription machinery, there is a general lack of specialized Plasmodium transcription factors.
Brief about the Study
PfGCN5 is a single GCN5 protein encoded by the genome of P. falciparum that features a long, unique N-terminal extension with no similarity to known protein domains and a conserved C-terminal HAT enzyme domain that can acetylate histone H3 at K9 and K14 in vitro During the IDC, PfGCN5 is present in its full-length form and is proteolytically digested by cysteine protease-like enzymes. PfGCN5 is required for the parasites’ IDC; hence, its role has been investigated via chemical suppression of its activity, which resulted in overall transcriptional disruption and a significant reduction in H3K9ac, indicating a possible connection between PfGCN5 and H3K9ac in the parasite. Recent efforts to find “readers” of the PTMs in P. falciparum resulted in the discovery of a putative PfGCN5-associated protein complex (or complexes) that differ significantly from the evolutionarily conserved SAGA complex.
The researchers defined a novel PfGCN5 complex using a tandem affinity purification (TAP) method and then performed functional studies on its main subunits. The importance of this PfGCN5 complex in regulating cellular and metabolic pathways important for parasite-specific activities including antigenic variation, erythrocyte invasion, and sexual development was discovered in this study.
Conclusion:
In the malaria parasite Plasmodium falciparum, epigenetic control of gene expression is critical for coordinating both general and parasite-specific cellular processes. We studied the histone acetyltransferase GCN5-mediated transcription regulation during the parasite’s intraerythrocytic development to learn more about its epigenetic processes.
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Reference:
- Miao, J., Wang, C., Lucky, A. B., Liang, X., Min, H., Adapa, S. R., Jiang, R., Kim, K., & Cui, L. (2021). A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion and virulence in the malaria parasite Plasmodium falciparum. PLOS Pathogens, 17(8), e1009351. https://doi.org/10.1371/journal.ppat.1009351
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Author info:
Soumya Shraddhya Paul is an undergrad biotechnology student who worked in building 3D prosthetics in Base Hospital Delhi Cantt, and holds a key interest in nutraceuticals and enzymology.
Publications:
- https://bioxone.in/news/worldnews/understanding-b-cell-genomics-to-fight-against-covid-19/
- https://bioxone.in/news/worldnews/the-current-ebola-epidemic-comes-to-an-end/
- https://bioxone.in/news/worldnews/an-improved-highly-resistant-tuberculosis-treatment-strategy/
- https://bioxone.in/news/worldnews/exosomes-role-in-lung-cancer-metastasis/
- https://bioxone.in/news/worldnews/depressive-disorders-and-pharmacotherapy-new-info-revealed/
Social Media Info: www.linkedin.com/in/soumya-shraddhya-paul-858229203
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