Role of PfMYST in DNA replication in Plasmodium falciparum

• Published in: Experimental parasitology 2022-11, Vol.242, p.108396-108396, Article 108396
• Main Authors: Shekhar, Shashank, Bhowmick, Krishanu, Dhar, Suman Kumar
• Format: Article
• Language: English
• Subjects: ARS; HAT; Histone H4K8Ac; MYST; Plasmodium; Replication
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2022.108396

Chromatin modification through histone acetylation/deacetylation is important for the regulation of transcription as well as DNA replication in eukaryotes. PfGCN5 and PfMYST are two well-studied histone acetyltransferases in Plasmodium. PfMYST containing the MYST domain, zinc finger domain, and the chromodomain primarily acetylates histone 4. Here, we show that PfMYST is expressed in two isoforms, a long version (∼72 kDa) and a short version (∼45 kDa) of the protein, while the shorter version is predominantly present in the nucleus. Further, the association of PfMYST with the putative Plasmodium autonomously replicating sequences (PfARS) was found to be much stronger than the binding of PfGCN5 in these regions with concomitant enrichment of the H4 acetylation level. The binding of PfMYST at these sites was also correlated with another replication protein PfORC1 as well as with the replicating stage (trophozoite) of the parasite. Collectively these results show for the first time the potential role of PfMYST in parasite DNA replication through chromatin modification that may be found useful for the intervention of parasite growth. •Two isoforms of PfMYST predominantly localize in distinct subcellular compartments.•PfMYST binds at previously reported PfARS regions.•PfMYST is significantly enriched at PfARS regions as compared to PfGCN5.•PfMYST binding at PfARS is associated with concomitant increase in H4K8Ac level.