論文

査読有り 国際誌
2017年4月10日

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

Scientific reports
  • 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

7
1
開始ページ
764
終了ページ
764
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-017-00714-7

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.

リンク情報
DOI
https://doi.org/10.1038/s41598-017-00714-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28396582
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429678

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