Potential mechanisms of aberrant DNA hypomethylation on the X chromosome in uterine leiomyomas

• Project/Area Number: 24592471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: SATO Shun 山口大学, 医学(系)研究科(研究院), 助教 (10534604)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮筋腫 / エピジェネティクス / DNAメチル化 / X染色体不活性化 / バイオマーカー

Outline of Final Research Achievements

Aberrant DNA hypomethylation in the whole X chromosome occurs in the uterine leiomyoma. In this study, we verified whether the aberrant expression of aberrantly hypomethylated genes specific to the leiomyoma or the dysfunction of genes related to the X chromosome inactivation (XCI) might be involved in the development of leiomyoma. As a result, although the two aberrantly hypomethylated genes specific to the leiomyoma on the X chromosome were identified, the aberrant expression did not occur in these genes. The expression analysis of XCI-related genes revealed that the expression of XIST and SATB1 genes tended to be altered similarly and was downregulated simultaneously in about a half of leiomyoma specimens. Therefore, the aberration of XCI-related genes such as SATB1 or XIST may be involved in aberrant hypomethylation on the X chromosome in a certain population of the patients with uterine leiomyomas.

Research Products

• [Journal Article] Genome-wide analysis of histone modifications in human endometrial stromal cells (2014)
  • Author(s): Tamura I, Ohkawa Y, Sato T, Suyama M, Jozaki K, Okada M, Lee L, Maekawa R, Asada H, Sato S, Yamagata Y, Tamura H, Sugino N
  • Journal Title: Mol. Endocrinol. Volume: 28 Issue: 10 Pages: 1656-1669
  • DOI: 10.1210/me.2014-1117
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential Mechanisms of Aberrant DNA Hypomethylation on the X Chromosome in Uterine Leiomyomas. (2014)
  • Author(s): Sato S, Maekawa R, Yamagata Y, Asada H, Tamura I, Lee L, Okada M, Tamura H, Sugino N.
  • Journal Title: J Reprod Dev. Volume: 60 Pages: 47-54
  • NAID: 130003381861
  • Peer Reviewed
• [Journal Article] Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells. (2014)
  • Author(s): Yamagata Y; Nishino K; Takaki E; Sato S; Maekawa R; Nakai A; Sugino N.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e83612-e83612
  • DOI: 10.1371/journal.pone.0083612
  • Peer Reviewed
• [Journal Article] Importance of C/EBPβ Binding and Histone Acetylation Status in the Promoter Regions for Induction of IGFBP-1, PRL, and Mn-SOD by cAMP in Human Endometrial Stromal Cells. (2014)
  • Author(s): Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, Asada H, Yamagata Y, Tamura H, Sugino N.
  • Journal Title: Endocrinology Volume: 155 Issue: 1 Pages: 275-286
  • DOI: 10.1210/en.2013-1569
  • Peer Reviewed
• [Journal Article] Genome-wide DNA methylation analysis reveals a potential mechanism for the pathogenesis and development of uterine leiomyomas. (2013)
  • Author(s): Maekawa R, Sato S, Yamagata Y, Asada H, Tamura I, Lee L, Okada M, Tamura H, Takaki E, Nakai A, Sugino N
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e66632-e66632
  • DOI: 10.1371/journal.pone.0066632
  • NAID: 120005652007
  • Peer Reviewed
• [Journal Article] Changes in Histone Modification and DNA Methylation of the StAR and Cyp19a1 Promoter Regions in Granulosa Cells Undergoing Luteinization during Ovulation In Rats (2013)
  • Author(s): Lee L
  • Journal Title: Endocrinology Volume: 154 Issue: 1 Pages: 458-470
  • DOI: 10.1210/en.2012-1610
  • Peer Reviewed
• [Presentation] 子宮筋腫におけるトランスクリプトームとエピゲノムを統合した蛋白質間相互ネットワーク解析 (2015)
  • Author(s): 前川亮，佐藤俊，浅田裕美，品川征大，岡田真紀，李理華，山縣芳明，田村博史，杉野法広
  • Organizer: 生殖内分泌学会
  • Place of Presentation: 大阪 千里ライフサイエンスセンター
  • Year and Date: 2015-01-10
• [Presentation] ラット顆粒膜細胞の黄体化に伴うCyp11a1(P450scc)遺伝子発現のepigenetics制御 (2015)
  • Author(s): 岡田真紀，李理華，品川征大，前川亮，浅田裕美，佐藤俊，山縣芳明，田村博史，杉野法広
  • Organizer: 生殖内分泌学会
  • Place of Presentation: 大阪 千里ライフサイエンスセンター
  • Year and Date: 2015-01-10
• [Presentation] 次世代シークエンサーを用いたヒト子宮内膜間質細胞 (ESC) の脱落膜化に伴うエピゲノム変化の解析 (2014)
  • Author(s): 杉野 法広, 田村 功, 城﨑 幸介, 品川 征大, 岡田 真紀, 李 理華, 浅田 裕美, 前川 亮, 佐藤 俊, 山縣 芳明, 田村 博史
  • Organizer: 日本繁殖生物学会
  • Place of Presentation: 北海道 帯広畜産大学
  • Year and Date: 2014-08-21 – 2014-08-24
• [Presentation] ヒト子宮内膜間質細胞 (ESC) の脱落膜化に伴いヒストン修飾とmRNA発現が上昇した遺伝子の検討 (2014)
  • Author(s): 城﨑 幸介, 田村 功, 品川 征大, 岡田 真紀, 李 理華, 浅田 裕美, 前川 亮, 佐藤 俊, 山縣 芳明, 田村 博史, 杉野 法広
  • Organizer: 日本繁殖生物学会
  • Place of Presentation: 北海道 帯広畜産大学
  • Year and Date: 2014-08-21 – 2014-08-24
• [Presentation] 子宮筋腫におけるX染色体の低メチル化変異機構 (2013)
  • Author(s): 佐藤俊，前川亮，山縣芳明，浅田裕美，田村功，李理華，岡田真紀，田村博史，杉野法広
  • Organizer: 第18回日本生殖内分泌学会学術集会
  • Place of Presentation: 東京砂防会館(東京都）
• [Presentation] ヒトESR1の組織特異的な転写開始点の使い分けに組織特異的DNAメチル化可変領域のメチル化が関与する (2013)
  • Author(s): 佐藤 俊・前川 亮・浅田裕美・田村 功・李 理華・岡田真紀・山縣芳明・杉野法広
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 奈良県新公会堂（奈良県）
• [Presentation] ヒトESR1の発現制御に関与する組織特異的DNAメチル化可変領域の同定 (2012)
  • Author(s): 佐藤俊
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 東京・学術総合センター