A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation

Abstract Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architec...

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Autores principales:	Sayaka Omori, Hideyuki Tanabe, Kimihiko Banno, Ayumi Tsuji, Nobutoshi Nawa, Katsuya Hirata, Keiji Kawatani, Chikara Kokubu, Junji Takeda, Hidetoshi Taniguchi, Hitomi Arahori, Kazuko Wada, Yasuji Kitabatake, Keiichi Ozono
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b025af64b00344728c5a37117dec64f6
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spelling	oai:doaj.org-article:b025af64b00344728c5a37117dec64f62021-12-02T12:32:12ZA Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation10.1038/s41598-017-00714-72045-2322https://doaj.org/article/b025af64b00344728c5a37117dec64f62017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00714-7https://doaj.org/toc/2045-2322Abstract Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.Sayaka OmoriHideyuki TanabeKimihiko BannoAyumi TsujiNobutoshi NawaKatsuya HirataKeiji KawataniChikara KokubuJunji TakedaHidetoshi TaniguchiHitomi ArahoriKazuko WadaYasuji KitabatakeKeiichi OzonoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sayaka Omori Hideyuki Tanabe Kimihiko Banno Ayumi Tsuji Nobutoshi Nawa Katsuya Hirata Keiji Kawatani Chikara Kokubu Junji Takeda Hidetoshi Taniguchi Hitomi Arahori Kazuko Wada Yasuji Kitabatake Keiichi Ozono A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
description	Abstract Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.
format	article
author	Sayaka Omori Hideyuki Tanabe Kimihiko Banno Ayumi Tsuji Nobutoshi Nawa Katsuya Hirata Keiji Kawatani Chikara Kokubu Junji Takeda Hidetoshi Taniguchi Hitomi Arahori Kazuko Wada Yasuji Kitabatake Keiichi Ozono
author_facet	Sayaka Omori Hideyuki Tanabe Kimihiko Banno Ayumi Tsuji Nobutoshi Nawa Katsuya Hirata Keiji Kawatani Chikara Kokubu Junji Takeda Hidetoshi Taniguchi Hitomi Arahori Kazuko Wada Yasuji Kitabatake Keiichi Ozono
author_sort	Sayaka Omori
title	A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
title_short	A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
title_full	A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
title_fullStr	A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
title_full_unstemmed	A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation
title_sort	pair of maternal chromosomes derived from meiotic nondisjunction in trisomy 21 affects nuclear architecture and transcriptional regulation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b025af64b00344728c5a37117dec64f6
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A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation

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