Functional analysis of the DNA region contributing to higher structure formation of chromosome

• Project/Area Number: 15K15076
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kanagawa Academy of Science and Technology
• Principal Investigator: Kondo Takashi 公益財団法人神奈川科学技術アカデミー, 未病改善食品評価法開発プロジェクト, 研究員 (40333299)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゲノム医化学 / 染色体立体配座 / 遺伝子発現制御 / 個体発生 / Meis2遺伝子座 / マウス / エピジェネティクス / 発生 / 遺伝子発現

Outline of Final Research Achievements

Recent studies suggest that three dimensional structures of chromosomes have important roles in transcriptional regulation or chromosomal replication, however, the mechanisms underlying forming chromosomal three dimensional structures remains unknown. In this work, we made attempt to understand the function of the DNA sequence that we found in a distance of 500 kb from Meis2 promoter and interacting to Meis2 promoter regardless of the transcriptional activity of Meis2.
We tried and succeeded to establish conditional knockout ES cells and mouse line in this funding period. We also found that this DNA region has impact to transcription activities of Meis2 promoter by the conditional deletion of this DNA region. This transcriptional pattern alterations are very complex and out of expectations, and thus the DNA region reveals that it is not simple enhancer sequence. And also, preliminary results suggest that entire knockout homozygotes are lethal in the very early stages (blastocyst?).

Research Products

• [Journal Article] Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species. (2016)
  • Author(s): Shinozaki F, Abe T, Kamei A, Watanabe Y, Yasuoka A, Shimada K, Kondo K, Arai S, Kumagai K, Kondo T, Abe K.
  • Journal Title: Genes Nutr. Volume: 11 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s12263-016-0534-2
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative deviating effects of maple syrup extract supplementation on the hepatic gene expression of mice fed a high-fat diet. (2016)
  • Author(s): Kamei, A., Watanabe, Y., Shinozaki, F., Yasuoka, A., Shimada, K., Kondo, K., Ishijima, T., Toyoda, T., Arai, S., Kondo, T., and Abe, K.
  • Journal Title: Mol. Nutr. Food Res. Volume: 61 Issue: 2 Pages: 1-15
  • DOI: 10.1002/mnfr.201600477
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression (2016)
  • Author(s): Yakushiji-Kaminatsui, N., Kondo, T., Endo, T.A., Koseki, Y., Kondo, K., Ohara, O., Vidal, M. and Koseki, H.
  • Journal Title: Development Volume: 143 Pages: 276-285
  • DOI: 10.1242/dev.127506
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Polycomb in transcriptional phase transition of developmental genes (2016)
  • Author(s): Kondo, T., Koseki, H. and Ito, S.
  • Journal Title: Trends Biochem. Sci. Volume: 41 Issue: 1 Pages: 9-19
  • DOI: 10.1016/j.tibs.2015.11.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Th17 Cell induction by adhesion of microbes to intestinal epithelial cells (2015)
  • Author(s): Atarashi, K., Tanoue, T., Ando. M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., Ishikawa, E., Shima, T., Hara, T., Kado, S., Jinnohara, T., Ohno, H., Kondo, T. et al.
  • Journal Title: Cell Volume: 163 Issue: 2 Pages: 367-380
  • DOI: 10.1016/j.cell.2015.08.058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Administration of a maple syrup extract to mitigate their hepatic inflammation induced by a high-fat diet: a transcriptome analysis (2015)
  • Author(s): Kamei, A., Watanabe, Y., Shinozaki, F., Yasuoka, A., Kondo, T., Ishijima, T., Toyoda, T., Arai, S. and Abe, K.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 18 Pages: 1-5
  • Peer Reviewed
• [Presentation] 高脂肪食摂取に対する応答性のマウス系統差 ― 網羅的遺伝子発現解析より (2016)
  • Author(s): 亀井飛鳥、渡部由貴、篠﨑文夏、安岡顕人、近藤香、嶋田耕育、阿部啓子、近藤隆
  • Organizer: 第70回日本栄養・食糧学会大会
  • Place of Presentation: 神戸
• [Presentation] Enhancer action on a developmental regulatory gene repressed by Polycomb (2016)
  • Author(s): 近藤隆、近藤香、椙下紘貴、伊藤伸介、阿部啓子、古関明彦
  • Organizer: 日本分子生物学会 2016年大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 発生遺伝子群のプロモーター制御において異性型Polycomb複合体は従来型と異なる活性を持つ (2015)
  • Author(s): 近藤 隆、近藤 香、椙下 紘貴、古関 明彦
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 機能性食品とエピジェネティクス (2015)
  • Author(s): 安岡 顕人, 嶋田 耕育, 亀井 飛鳥, 篠崎 文夏, 近藤 香, 近藤 隆, 三坂 巧, 岡田 晋治, 阿部 啓子
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 異性型ポリコーム複合体構成因子の欠損がES細胞の分化に与える影響 (2015)
  • Author(s): 椙下 紘貴、近藤 隆、伊藤 伸介、近藤 香、古関 明彦
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2015-12-01