5 years ago

Histone methyltransferase 1 regulates the encystation process in the parasite Giardia lamblia

Histone methyltransferase 1 regulates the encystation process in the parasite Giardia lamblia
Andrea S. Rópolo, Gonzalo F. Mayol, Natacha Zlocowski, Agostina Salusso, Nahuel Zamponi
In eukaryotes, histone lysine methylation is associated with either active or repressed chromatin states, depending on the status of methylation. Even when the amino-terminus of Giardia lamblia histones diverges from other organisms, these regions contain lysine residues that are potential targets for methylation. When we examined the role of the histone methyltransferase 1 (HMT1) in the regulation of the encystation process by giardial histone methyltransferase 1 (GlHMT1) overexpression or downregulation, we observed an increase or a decrease in cyst production, respectively, compared to wild-type trophozoites. A time-lapse analysis of encystation showed that overexpression of GlHMT1 induced an earlier and faster process than in wild-type cells together with an upregulation of mRNA expression of cyst wall proteins. Subcellular localization studies indicated that GlHMT1-hemaglutinin was mainly associated with the nuclear and perinuclear region in both growing and encysting parasites, in agreement with bioinformatics analyses showing that GlHMT-1 possesses nuclear localization signals in addition to the classical SU(var)3-9, Enhancer-of-Zeste, Trithorax (SET), and post-SET domains. Altogether, these findings suggest that the function of HMT1 is critical for the success and timing of the encystation process, and reinforce the idea that epigenetic marks are critical for cyst formation in G. lamblia. Giardia lamblia differentiation is critical for the transmission of giardiasis. During this process we found that the enzyme giardial histone methyltransferase 1 is involved in the upregulation of the genes related to cyst wall formation, reinforcing the idea that epigenetic marks as critical players during G. lamblia encystation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14131

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