Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in...

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Main Authors: V. V. Demeneva, E. N. Tolmacheva, T. V. Nikitina, E. A. Sazhenova, S. Yu. Yuriev, A. Sh. Makhmutkhodzhaev, A. S. Zuev, S. A. Filatova, A. E. Dmitriev, Ya. A. Darkova, L. P. Nazarenko, I. N. Lebedev, S. A. Vasilyev
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2023-03-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/3633
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author V. V. Demeneva
E. N. Tolmacheva
T. V. Nikitina
E. A. Sazhenova
S. Yu. Yuriev
A. Sh. Makhmutkhodzhaev
A. S. Zuev
S. A. Filatova
A. E. Dmitriev
Ya. A. Darkova
L. P. Nazarenko
I. N. Lebedev
S. A. Vasilyev
author_facet V. V. Demeneva
E. N. Tolmacheva
T. V. Nikitina
E. A. Sazhenova
S. Yu. Yuriev
A. Sh. Makhmutkhodzhaev
A. S. Zuev
S. A. Filatova
A. E. Dmitriev
Ya. A. Darkova
L. P. Nazarenko
I. N. Lebedev
S. A. Vasilyev
author_sort V. V. Demeneva
collection DOAJ
description The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p < 0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 – R = –0.59, YWHAB – R = –0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 – R = –0.46, YWHAB – R = –0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.
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publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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spelling doaj-art-5a1a5fd8039a49aa8d6121a82b380e402025-02-01T09:58:11ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-03-01271637110.18699/VJGB-23-091330Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancyV. V. Demeneva0E. N. Tolmacheva1T. V. Nikitina2E. A. Sazhenova3S. Yu. Yuriev4A. Sh. Makhmutkhodzhaev5A. S. Zuev6S. A. Filatova7A. E. Dmitriev8Ya. A. Darkova9L. P. Nazarenko10I. N. Lebedev11S. A. Vasilyev12Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesSiberian State Medical UniversitySiberian State Medical UniversityResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesNational Research Tomsk State UniversityNational Research Tomsk State UniversityNational Research Tomsk State UniversityResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State UniversityThe placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p < 0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 – R = –0.59, YWHAB – R = –0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 – R = –0.46, YWHAB – R = –0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.https://vavilov.elpub.ru/jour/article/view/3633miscarriageplacentaretrotransposon line-1dna methylationnup153ywhab
spellingShingle V. V. Demeneva
E. N. Tolmacheva
T. V. Nikitina
E. A. Sazhenova
S. Yu. Yuriev
A. Sh. Makhmutkhodzhaev
A. S. Zuev
S. A. Filatova
A. E. Dmitriev
Ya. A. Darkova
L. P. Nazarenko
I. N. Lebedev
S. A. Vasilyev
Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
Вавиловский журнал генетики и селекции
miscarriage
placenta
retrotransposon line-1
dna methylation
nup153
ywhab
title Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
title_full Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
title_fullStr Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
title_full_unstemmed Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
title_short Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy
title_sort expression of the nup153 and ywhab genes from their canonical promoters and alternative promoters of the line 1 retrotransposon in the placenta of the first trimester of pregnancy
topic miscarriage
placenta
retrotransposon line-1
dna methylation
nup153
ywhab
url https://vavilov.elpub.ru/jour/article/view/3633
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