Coordinated epigenetic regulation of cell type-specific genes and chronic disease development in cardiomyocytes.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24689037
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Keio University
• Principal Investigator: ODA Mayumi 慶應義塾大学, 医学部, 助教 (80567511)
• Research Collaborator: SAKOTA Miki 慶應義塾大学, 医学部, 研究員
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: エピゲノム / DNAメチル化 / 細胞特異的発現遺伝子 / 成熟細胞 / DNA脱メチル化機構 / 病態発生 / エピジェネティック制御 / gene body領域

Research Abstract

In this study, I made several cell type-specific DNA methylation epigenome data of isolated cardiomyocyte populations from several developmental stages and pushed forward understanding of the epigenome in matured cells. I compared the cardiomyocyte epigenome with those of embryonic stem cells and liver, and also with the heart failure cardiac muscle cells. As the result, small subpopulation of genes with remarkable DNA methylation changes in their gene body regions were included in the cell type-specific gene trait. These gene body regions accumulated the transcription machinery and histone acetylation enzyme in the matured cells, and transiently accumulate the derivatives of methyl cytosine demethylation, which implicates the active demethylation process. Our study showed the involvement of the active DNA demethylation process in gene body regions and indicates the possibility that the gene body DNA hypomethylationmay stabilize the cell type-specific gene transcription.

Research Products

• [Journal Article] Genetic analysis of essential cardiac transcription factors in 256 patients with non-syndromic congenital heart defects (2012)
  • Author(s): Kodo K, Nishizawa T, Furutani M, Arai S, Ishihara K, Oda M, Makino S, Fukuda K, Takahashi T, Matsuoka R, Nakanishi T, Yamagishi H
  • Journal Title: Circulation journal : official journal of the Japanese Circulation Society Volume: 76 Pages: 1703-1711
  • DOI: 10.1253/circj.CJ-11-1389
  • Peer Reviewed
• [Presentation] 成熟細胞の細胞特異的遺伝子gene body領域における能動的DNA脱メチル化分子機構の関与 (2014)
  • Author(s): 小田真由美
  • Organizer: 第8回エピジェネティクス研究会年会
  • Place of Presentation: 伊藤国際学術研究センター(東京都)(ポスター発表)
  • Year and Date: 20140525-27
• [Presentation] DNAメチル化エピゲノム解析による哺乳類gene body DNAメチル化の成り立ちと転写の関係 (2013)
  • Author(s): 小田真由美
  • Organizer: NGS現場の会第三回研究会
  • Place of Presentation: 神戸国際会議腸(兵庫県)(ポスター発表)
  • Year and Date: 20130904-05
• [Presentation] DNAメチル化エピゲノムによるアクセシビリティ調節と細胞特異的遺伝子発現の効率化 (2013)
  • Author(s): 小田真由美
  • Organizer: 第7回エピジェネティクス研究会年会
  • Place of Presentation: 奈良県新公会堂(奈良県)(ポスター発表)
  • Year and Date: 20130530-31
• [Presentation] Cell Type-specific Gene body DNA Hypomethylation Contributes to Transcriptional Efficiency in Cardiomyocyte Maturation (2012)
  • Author(s): Mayumi Oda
  • Organizer: 第6回エピジェネティクス研究会年会
  • Place of Presentation: 一橋学術総合センター(東京都)(ポスター発表)
  • Year and Date: 20120514-15
• [Presentation] Escape of Gene Body DNA Methylation in Cardiac Genes is Cooperative With the Cell Type-specific Expression Patterns (2012)
  • Author(s): Mayumi Oda
  • Organizer: Weinstein meeting 2012
  • Place of Presentation: Sheraton Chicago Hotel and Towers(シカゴ・イリノイ州・米国)(口頭発表)
  • Year and Date: 20120502-15
• [Remarks] 坂口講座テニュアトラック・プログラム
  • URL: http://www.careerpath-prj.keio.ac.jp/sakaguchi/scholar/m_oda/
• [Remarks] 義塾大学医学部・システム医学講座
  • URL: http://systemsmedicine.jp