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KMID : 0425120240620010098
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Parasites, Hosts and Diseases
2024 Volume.62 No. 1 p.98 ~ p.116
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Genome-wide identification of histone lysine methyltransferases and their implications in the epigenetic regulation of eggshell formation-related genes in a trematode parasite Clonorchis sinensis
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Park Min-Ji
Sohn Woon-Mok
Bae Young-An
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Abstract
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Epigenetic writers including DNA and histone lysine methyltransferases (DNMT andHKMT, respectively) play an initiative role in the differentiation and development of eukaryotic organisms through the spatiotemporal regulation of functional gene expressions. However, the epigenetic mechanisms have long been suspected in helminth parasites lacking the major DNA methyltransferases DNMT1 and DNMT3a/3b. Very little information on the evolutionary status of the epigenetic tools and their role in regulatingchromosomal genes is currently available in the parasitic trematodes. We previouslysuggested the probable role of a DNMT2-like protein (CsDNMT2) as a genuine epigenetic writer in a trematode parasite Clonorchis sinensis. Here, we analyzed the phylogenyof HKMT subfamily members in the liver fluke and other platyhelminth species. Theplatyhelminth genomes examined conserved genes for the most of SET domain-containing HKMT and Disruptor of Telomeric Silencing 1 subfamilies, while some geneswere expanded specifically in certain platyhelminth genomes. Related to the high genedosages for HKMT activities covering differential but somewhat overlapping substratespecificities, variously methylated histones were recognized throughout the tissues/organs of C. sinensis adults. The temporal expressions of genes involved in eggshell formation were gradually decreased to their lowest levels proportionally to aging, whereasthose of some epigenetic tool genes were re-boosted in the later adult stages of theparasite. Furthermore, these expression levels were significantly affected by treatmentwith DNMT and HKMT inhibitors. Our data strongly suggest that methylated histonesare potent epigenetic markers that modulate the spatiotemporal expressions of C. sinensis genes, especially those involved in sexual reproduction.
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KEYWORD
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Clonorchis sinensis, epigenetics, DNMT2-only organism, histone lysine methyltransferase, histone methylation, methyltransferase inhibitor
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