Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i>
Epigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. Our investigation identifies and functionally characterizes the orthologue of S-adenosylmethionine (SAM) binding methyltransferase enzyme, disruptor of telomeric sil...
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doaj-2f8438b21fdc47b5bebbaf65e47067462020-11-25T02:33:57ZengMDPI AGVaccines2076-393X2020-04-01815715710.3390/vaccines8020157Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i>Julia Gobl0Deepak Kumar Sinha1Radek Sima2Jan Perner3Petr Kopáček4James J Valdés5Ryan O. M. Rego6Alejandro Cabezas-Cruz7Faculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicFaculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicFaculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicInstitute of Parasitology, Biology Center, Czech Academy of Sciences, 37005 České Budějovice, Czech RepublicFaculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicFaculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicFaculty of Science, University of South Bohemia, 37005 České Budějovice, Czech RepublicUMR BIPAR, INRAE, ANSES, Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceEpigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. Our investigation identifies and functionally characterizes the orthologue of S-adenosylmethionine (SAM) binding methyltransferase enzyme, disruptor of telomeric silencing 1-like (DOT1L) in <i>Ornithodoros moubata</i> (OmDOT1L), a soft tick vector for the relapsing fever pathogen <i>Borrelia duttonii</i> and the African swine fever virus. The OmDOT1L tertiary structure was predicted and compared to the <i>Homo sapiens</i> DOT1L which had been co-crystalized with SGC0946, a DOT1L-specific inhibitor. The amino acid residues crucial for SAM and SGC0946 binding conserved in most DOT1L sequences available, are also conserved in OmDOT1L. Quantitative PCR of <i>Omdot1l</i> during <i>O. moubata</i> life stages showed that transcripts were significantly upregulated in first-stage nymphs. <i>O. moubata</i> larvae exposed to SGC0946 displayed high mortality during molting to first-stage nymphs. Furthermore, a significant decrease in weight was observed in second-stage nymphs fed on recombinant OmDOT1L-immunized rabbits. In contrast, artificial blood feeding supplemented with SGC0946 did not affect survival and reproductive performance of adult female ticks. We concluded that OmDOT1L plays an essential role in the regulation of larval molting and the feeding of <i>O. moubata</i> second-stage nymphs.https://www.mdpi.com/2076-393X/8/2/157<i>Ornithodoros moubata</i>histone methyltransferaseDOT1L |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Gobl Deepak Kumar Sinha Radek Sima Jan Perner Petr Kopáček James J Valdés Ryan O. M. Rego Alejandro Cabezas-Cruz |
spellingShingle |
Julia Gobl Deepak Kumar Sinha Radek Sima Jan Perner Petr Kopáček James J Valdés Ryan O. M. Rego Alejandro Cabezas-Cruz Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> Vaccines <i>Ornithodoros moubata</i> histone methyltransferase DOT1L |
author_facet |
Julia Gobl Deepak Kumar Sinha Radek Sima Jan Perner Petr Kopáček James J Valdés Ryan O. M. Rego Alejandro Cabezas-Cruz |
author_sort |
Julia Gobl |
title |
Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> |
title_short |
Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> |
title_full |
Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> |
title_fullStr |
Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> |
title_full_unstemmed |
Histone Methyltransferase DOT1L Is Involved in Larval Molting and Second Stage Nymphal Feeding in <i>Ornithodoros moubata</i> |
title_sort |
histone methyltransferase dot1l is involved in larval molting and second stage nymphal feeding in <i>ornithodoros moubata</i> |
publisher |
MDPI AG |
series |
Vaccines |
issn |
2076-393X |
publishDate |
2020-04-01 |
description |
Epigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. Our investigation identifies and functionally characterizes the orthologue of S-adenosylmethionine (SAM) binding methyltransferase enzyme, disruptor of telomeric silencing 1-like (DOT1L) in <i>Ornithodoros moubata</i> (OmDOT1L), a soft tick vector for the relapsing fever pathogen <i>Borrelia duttonii</i> and the African swine fever virus. The OmDOT1L tertiary structure was predicted and compared to the <i>Homo sapiens</i> DOT1L which had been co-crystalized with SGC0946, a DOT1L-specific inhibitor. The amino acid residues crucial for SAM and SGC0946 binding conserved in most DOT1L sequences available, are also conserved in OmDOT1L. Quantitative PCR of <i>Omdot1l</i> during <i>O. moubata</i> life stages showed that transcripts were significantly upregulated in first-stage nymphs. <i>O. moubata</i> larvae exposed to SGC0946 displayed high mortality during molting to first-stage nymphs. Furthermore, a significant decrease in weight was observed in second-stage nymphs fed on recombinant OmDOT1L-immunized rabbits. In contrast, artificial blood feeding supplemented with SGC0946 did not affect survival and reproductive performance of adult female ticks. We concluded that OmDOT1L plays an essential role in the regulation of larval molting and the feeding of <i>O. moubata</i> second-stage nymphs. |
topic |
<i>Ornithodoros moubata</i> histone methyltransferase DOT1L |
url |
https://www.mdpi.com/2076-393X/8/2/157 |
work_keys_str_mv |
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