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著作: HItomi Matsuzaki/[岡村 永一]/Takuya Takahashi/Aki Ushiki/Toshinobu Nakamura/Toru Nakano/Kenichiro Hata/Akiyoshi Fukamizu/Keiji Tanimoto/De novo DNA methylation through the 5'-segment of the H19 ICR maintains its imprint during early embryogenesis./[Development]

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EID
306646
EOID
820977
Map
0
LastModified
2016年5月24日(火) 18:02:07
Operator
岡村 永一
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TRUE
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Owner
岡村 永一
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) HItomi Matsuzaki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 岡村 永一
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Takuya Takahashi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Aki Ushiki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Toshinobu Nakamura
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Toru Nakano
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Kenichiro Hata
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Akiyoshi Fukamizu
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. (英) Keiji Tanimoto
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) De novo DNA methylation through the 5'-segment of the H19 ICR maintains its imprint during early embryogenesis.

副題 任意
要約 任意

(英) Genomic imprinting is a major monoallelic gene expression regulatory mechanism in mammals, and depends on gamete-specific DNA methylation of specialized cis-regulatory elements called imprinting control regions (ICRs). Allele-specific DNA methylation of the ICRs is faithfully maintained at the imprinted loci throughout development, even in early embryos where genomes undergo extensive epigenetic reprogramming, including DNA demethylation, to acquire totipotency. We previously found that an ectopically introduced H19 ICR fragment in transgenic mice acquired paternal allele-specific methylation in the somatic cells of offspring, whereas it was not methylated in sperm, suggesting that its gametic and postfertilization modifications were separable events. We hypothesized that this latter activity might contribute to maintenance of the methylation imprint in early embryos. Here, we demonstrate that methylation of the paternally inherited transgenic H19 ICR commences soon after fertilization in a maternal DNMT3A- and DNMT3L-dependent manner. When its germline methylation was partially obstructed by insertion of insulator sequences, the endogenous paternal H19 ICR also exhibited postfertilization methylation. Finally, we refined the responsible sequences for this activity in transgenic mice and found that deletion of the 5' segment of the endogenous paternal H19 ICR decreased its methylation after fertilization and attenuated Igf2 gene expression. These results demonstrate that this segment of the H19 ICR is essential for its de novo postfertilization DNA methylation, and that this activity contributes to the maintenance of imprinted methylation at the endogenous H19 ICR during early embryogenesis.

キーワード 推奨
  1. (英) Animals
  2. (英) Base Sequence
  3. (英) Blotting, Southern
  4. (英) DNA (Cytosine-5-)-Methyltransferase
  5. (英) DNA Methylation
  6. (英) DNA Primers
  7. (英) Embryonic Development
  8. (英) Female
  9. (英) Gene Expression Regulation, Developmental
  10. (英) Genomic Imprinting
  11. (英) Insulin-Like Growth Factor II
  12. (英) Male
  13. (英) Mice
  14. (英) Mice, Transgenic
  15. (英) Molecular Sequence Data
  16. (英) RNA, Long Noncoding
  17. (英) Reverse Transcriptase Polymerase Chain Reaction
  18. (英) Sequence Analysis, DNA
発行所 推奨
誌名 必須 Development([The Company of Biologists Limited])
(pISSN: 0950-1991, eISSN: 1477-9129)
ISSN 任意 1477-9129
ISSN: 0950-1991 (pISSN: 0950-1991, eISSN: 1477-9129)
Title: Development (Cambridge, England)
Title(ISO): Development
Publisher: Company of Biologists
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 142
必須 22
必須 3833 3844
都市 任意
年月日 必須 2015年 9月 28日
URL 任意
DOI 任意 10.1242/dev.126003    (→Scopusで検索)
PMID 任意 26417043    (→Scopusで検索)
CRID 任意
WOS 任意 000366361300005
Scopus 任意 2-s2.0-84947483852
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.1242/dev.126003

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

  4. (英) KeywordList.Keyword: DNA methylation

  5. (英) KeywordList.Keyword: Early embryogenesis

  6. (英) KeywordList.Keyword: Genomic imprinting

  7. (英) KeywordList.Keyword: Igf2/H19 locus