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Last Updated: 18/06/2024
Elucidation of the mechanism of establishment of de novo heterochromatin in Plasmodium malaria
Objectives
This study aims to elucidate the mechanism that induces heterochromatinization that regulates the expression of the master gene AP2-G, which plays a role in the differentiation of malaria parasite sexual germ cells (gametocytes).
Eukaryotic genomic DNA contains highly condensed heterochromatin regions, some of which are known to regulate specific gene expression. In general, heterochromatin, which is involved in gene regulation, is based on histone H3K27 methylation, and it has been suggested that malaria parasites construct and release H3K9-based heterochromatin as required. In 2021, the reporter gene mNeongreen (mNG), which is the AP2-G promoter (AP2-Gpro) linked to the AP2-Gdel protozoan strain that completely removes the locus containing the heterochromatin region of the Ap2-G gene, will be used as an artificial chromosome. There has been success in constructing an assay system that can evaluate AP2-Gpro::mNG expression and heterochromatinization on artificial chromosomes. As a result of comparison with the negative control Cam::mNG linked with the promoter of a heterologous gene, cells with no mNG signal were frequently observed in the AP2-Gpro::mNG-introduced strain. This result suggests the possibility that the AP2-G promoter on the artificial chromosome is also epigenetically repressed, like the AP2-G gene on the original chromosome. From the next fiscal year, the plan is to analyze heterochromatin markers (histone H3K9 methylation, HP1 protein binding, etc.) in artificial chromosomes.
Apr 2021 — Mar 2024
$35,721