Search for germline epigenetic information that induces post-fertilization imprinted methylation

• Project/Area Number: 17H05012
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Genetics/Chromosome dynamics
• Research Institution: University of Tsukuba
• Principal Investigator: Matsuzaki Hitomi 筑波大学, 生命環境系, 助教 (50436242)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: エピジェネティクス / ゲノム刷り込み / DNAメチル化 / 遺伝子 / 発現制御

Outline of Final Research Achievements

In mammals, mono-allelic expression of a subset of genes (genomic imprinting) is essential for normal development, which is governed by allele-specific DNA methylation at the imprinting control regions (ICRs) within the loci. In the present study, I searched for epigenetic information used to discriminate parental alleles in the process of post-fertilization imprinted DNA methylation of the ICR at the Igf2/H19 locus. In addition, I identified cis sequences which are necessary and sufficient for the regulation.

Academic Significance and Societal Importance of the Research Achievements

ヒトでは、刷り込み遺伝子のDNAメチル化異常による疾患が知られている。また、近年、親が曝された環境要因によりエピジェネティックな変化が配偶子で生じ、子での遺伝子発現に影響を与える可能性も指摘されている。本研究による、受精後のアリル特異的DNAメチル化制御メカニズムの解析結果は、疾患の原因究明やエピジェネティック遺伝の実体の解明に向けて、基礎となる情報を提供できると期待される。

Research Products

• [Journal Article] Recapitulation of gametic DNA methylation and its post-fertilization maintenance with reassembled DNA elements at the mouse Igf2/H19 locus (2020)
  • Author(s): Matsuzaki, H., Kuramochi, D., Okamura, E., Hirakawa, K., Ushiki, A., and Tanimoto, K.
  • Journal Title: Epigenetics & Chromatin Volume: 13 Pages: 2-2
  • DOI: 10.1186/s13072-019-0326-1
  • Peer Reviewed / Open Access
• [Journal Article] Synthetic DNA fragments bearing ICR cis elements become differentially methylated and recapitulate genomic imprinting in transgenic mice (2018)
  • Author(s): Matsuzaki, H,. Okamura, E., Kuramochi, D., Ushiki, A., Hirakawa, K., Fukamizu, A., and Tanimoto, K.
  • Journal Title: Epigenetics & Chromatin Volume: 11 Pages: 36-36
  • DOI: 10.1186/s13072-018-0207-z
  • NAID: 120006501410
  • Peer Reviewed / Open Access
• [Presentation] Reconstituted H19 ICR sequence with identified cis elements is capable of maintaining genomic imprinting in knock-in mouse (2019)
  • Author(s): Matsuzaki, H., Kuramochi, D., Hirakawa, K., and Tanimoto, K.
  • Organizer: 33rd International Mammalian Genome Conference
  • Int'l Joint Research
• [Presentation] Test for imprinted DNA methylation activity of the human H19-ICR in YAC transgenic mice by adopting a transgene co-placement strategy (2019)
  • Author(s): Hirakawa, K., Matsuzaki, H., and Tanimoto, K
  • Organizer: The 15th Transgenic Technology Meeting
  • Int'l Joint Research
• [Presentation] マウスのゲノム刷り込み制御におけるH19-ICR配列反転の効果 (2019)
  • Author(s): 宮嶋優、谷本啓司、松崎仁美
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] YACトランスジェニック・マウスを用いたヒトH19-ICR刷り込みメチル化メカニズムの検証 (2019)
  • Author(s): 平川勝彦、松崎仁美、谷本啓司
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] In vivo analysis of H19 gene transcriptional mechanism by inversion of the H19 imprinting control region (2018)
  • Author(s): Matsuzaki, H., Miyajima, Y., and Tanimoto, K
  • Organizer: 32nd International Mammalian Genome Conference
  • Int'l Joint Research
• [Presentation] H19-ICR反転によるH19遺伝子転写制御機構のin vivo解析 (2018)
  • Author(s): 宮嶋優、谷本啓司、松崎仁美
  • Organizer: 第12回日本エピジェネティクス研究会年会
• [Presentation] ヒトβグロビン遺伝子座におけるH19-ICR断片挿入の効果とクロマチン立体構造解析 (2018)
  • Author(s): 平川勝彦、松﨑仁美、谷本啓司
  • Organizer: 第12回日本エピジェネティクス研究会年会
• [Presentation] H19-ICR 反転マウスを用いたゲノム刷り込み制御機構の解析 (2018)
  • Author(s): 松﨑仁美、宮嶋優、谷本啓司
  • Organizer: 第41回日本分子生物学会年会