Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Exp Parasitol. 2022 Nov;242:108396. doi: 10.1016/j.exppara.2022.108396. Epub 2022 Oct 11.
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.
通过组蛋白乙酰化/去乙酰化进行染色质修饰对于真核生物中转录和 DNA 复制的调控非常重要。PfGCN5 和 PfMYST 是疟原虫中两种研究得很好的组蛋白乙酰转移酶。PfMYST 包含 MYST 结构域、锌指结构域和 chromodomain，主要乙酰化组蛋白 4。在这里，我们表明 PfMYST 以两种同工型表达，一种是蛋白质的长版本（72 kDa），另一种是短版本（45 kDa），而较短的版本主要存在于核内。此外，PfMYST 与假定的疟原虫自主复制序列（PfARS）的结合比 PfGCN5 在这些区域的结合要强得多，同时伴随着 H4 乙酰化水平的富集。PfMYST 在这些位点的结合也与另一个复制蛋白 PfORC1 以及寄生虫的复制阶段（滋养体）相关。总的来说，这些结果首次表明 PfMYST 通过染色质修饰在寄生虫 DNA 复制中可能发挥作用，这可能对寄生虫生长的干预有用。
