Elucidation of transcription factory that is associated with the transcriptional regulation of the ABO gene.

• Project/Area Number: 25860486
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Gunma University
• Principal Investigator: TAKAHASHI Yoichiro 群馬大学, 医学(系)研究科(研究院), 助教 (50640538)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ABO / 血液型 / 血液型亜型 / 転写調節 / エンハンサー / 細胞分化 / ヒストン脱アセチル化酵素 / サイレンサー

Outline of Final Research Achievements

1) We identified novel genetic mutation responsible for the blood group subtype Am, and clarified association of transcriptional factor RUNX1. 2) We identified novel genetic mutations responsible for the blood group subtype A3 or B3. 3) We identified candidate regions that possess potential enhancer activity for the ABO expression. 4) It was clarified that the transcription of the ABO gene is regulated by epigenetic mechanism, and some reagent could alter the expression level of ABO.

Research Products

• [Journal Article] BO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination. (2016)
  • Author(s): Nakajima T, Sano R, Takahashi Y, Watanabe K, Kubo R, Kobayashi M, Takahashi K, Takeshita H, Kominato Y.
  • Journal Title: Vox Sang. Volume: 11 Issue: 1 Pages: 90-92
  • DOI: 10.1111/vox.12312
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ABO遺伝子の転写調節領域の変異により血液型亜型Am型、A3型、B3型が生じる. (2015)
  • Author(s): 高橋遥一郎, 佐野利恵, 中島たみ子, 小湊慶彦.
  • Journal Title: DNA多型 Volume: 23 Pages: 103-107
  • Peer Reviewed
• [Journal Article] Blood group gene is barely expressed in vitro erythroid culture of Bm-derived CD34+ cells without an erythroid cell-specific regulatory element (2015)
  • Author(s): Sano R, Nogawa T, Nakajima T, Takahashi Y, Kubo R, Kominato Y, Yokohama A, Tsukada J, Yamao H, Kishida T, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 108 Issue: 3 Pages: 302-309
  • DOI: 10.1111/vox.12220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A 3.0-kb delation including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype (2015)
  • Author(s): Sano R, Kuboya E, Nakajima T, Takahashi Y, Takahashi K, Kubo R, Kominato Y, Takeshita H, Yamao H, Kishida T, Isa K, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 108 Issue: 3 Pages: 310-313
  • DOI: 10.1111/vox.12216
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell-specific enhancer-like element and the ABO promoter in individuals with phenotypes A3 and B3, respectively (2014)
  • Author(s): Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Michino J, Masuno A, Tsuneyama H, Ito S, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 107 Issue: 2 Pages: 171-180
  • DOI: 10.1111/vox.12136
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ABO chimerism with a minor allele detected by the peptide nucleic acid-mediated polymerase chain reaction clamping method. (2014)
  • Author(s): Sano R, Takahashi Y, Nakajima T, Yoshii M, Kubo R, Takahashi K, Kominato Y, Takeshita H, Yasuda T, Tsuneyama H, Uchikawa M, Isa K, Ogasawara K.
  • Journal Title: Blood Transfusion Volume: 12 Pages: 431-434
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ABO遺伝子内血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例 (2014)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子, 久保谷江里, 小湊慶彦, 藤原純子, 竹下治男, 安田年博, 岸田哲子
  • Journal Title: DNA多型 Volume: 22 Pages: 109-113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deletion of the RUNX1 binding site in the erythroid cell-specific regulatory element of the ABO gene in two individuals with the Am phenotype. (2014)
  • Author(s): Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Tsuneyama H, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 106 Issue: 2 Pages: 167-175
  • DOI: 10.1111/vox.12077
  • Peer Reviewed / Open Access
• [Journal Article] Mutation of the GATA site in the erythroid cell-specific regulatory element of the ABO gene in a Bm subgroup individual (2013)
  • Author(s): Tamiko Nakajima
  • Journal Title: Transfusion Volume: 53 Issue: 11pt2 Pages: 2917-2927
  • DOI: 10.1111/trf.12181
  • Peer Reviewed
• [Journal Article] ABO式血液型遺伝子エンハンサー欠損がBm型の原因である. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 小湊慶彦.
  • Journal Title: DNA多型 Volume: 21 Pages: 122-126
  • Peer Reviewed
• [Presentation] Bm型では赤血球系細胞においてB遺伝子の発現が極めて低下している. (2015)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 小湊慶彦.
  • Organizer: 日本DNA多型学会第24回学術集会
  • Place of Presentation: 岡山大学津島キャンパス（岡山）
  • Year and Date: 2015-11-20
• [Presentation] Bm型では赤血球系細胞においてB遺伝子発現が極めて低下している―CD34陽性細胞を用いた分化培養実験―. (2015)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 竹下治男, 安田年博, 岸田哲子, 小湊慶彦.
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 文化プラザかるぽーと（高知）
  • Year and Date: 2015-06-11
• [Presentation] ABO遺伝子の転写調節領域の変異により血液型亜型Am型、A3型、B3型が生じる (2014)
  • Author(s): 高橋遥一郎, 佐野利恵, 中島たみ子, 小湊慶彦.
  • Organizer: 日本DNA多型学会第23回学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-26 – 2014-11-27
• [Presentation] Mutations were found in the transcription-regulatory elements such as the promoter and the erythroid cell-specific enhancer of ABO in individuals with phenotypes Am, A3 and B3. (2014)
  • Author(s): Takahashi Y, Sano R, Nakajima T, Takeshita H, Yasuda T, Kominato Y.
  • Organizer: 9th International Symposium on Advances in Legal Medicine (ISALM).
  • Place of Presentation: Ｆｕｋｕｏｋａ
  • Year and Date: 2014-06-16 – 2014-06-20
• [Presentation] ABO chimerism with a minor allele detected by the PNA－mediated PCR clamping method. (2014)
  • Author(s): Sano R, Takahashi Y, Nakajima T, Yoshii M, Kubo R, Takahashi K, Kominato Y, Takeshita H, Yasuda T.
  • Organizer: 9th International Symposium on Advances in Legal Medicine (ISALM).
  • Place of Presentation: Ｆｕｋｕｏｋａ
  • Year and Date: 2014-06-16 – 2014-06-20
• [Presentation] BLOOD GROUP B GENE EXPRESSION IS SHARPLY REDUCED IN THE ERYTHROID-LINEAGE PROGENITOR CELLS OF A B(M) INDIVIDUAL WITH DELETION OF AN ERYTHROID CELL-SPECIFIC ENHANCER. (2014)
  • Author(s): Sano R, Nogawa M, Nakajima T, Takahashi Y, Kominato Y, Takeshita H, Yasuda T, Yokohama A, Yamao H, Kishida T, Isa K, Ogasawara K and Uchikawa M.
  • Organizer: 33rd International Congress of the International Society of Blood Transfusion
  • Place of Presentation: Ｓｅｏｕｌ
  • Year and Date: 2014-06-01 – 2014-06-05
• [Presentation] MUTATION OF THE TRANSCRIPTION REGULATION REGIONS IN THE ABO GENE ACCOUNTING FOR A3 AND B3 PHENOTYPES. (2014)
  • Author(s): Isa K, Ogasawara K, Ito S, Tsuneyama H, Yabe R, Takahashi Y, Sano R, Nakajima T, Kominato Y, Uchikawa M, Satake M and Tadokoro K.
  • Organizer: 33rd International Congress of the International Society of Blood Transfusion
  • Place of Presentation: Ｓｅｏｕｌ
  • Year and Date: 2014-06-01 – 2014-06-05
• [Presentation] 赤血球系細胞特異的な転写制御領域に一塩基置換を認めたA3型. (2014)
  • Author(s): 伊藤正一, 荻山佳子, 高橋美都保, 小原健良, 伊藤孝, 常山初江, 伊佐和美, 小笠原健一, 内川誠, 高橋遥一郎, 佐野利恵, 中島たみ子,小湊慶彦.
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] ABOプロモーター領域に変異を認めたB3型‐ABO遺伝子全長PCR法による解析‐. (2014)
  • Author(s): 伊佐和美, 小笠原健一, 佐竹正博, 田所憲治, 伊藤正一, 常山初江, 矢部隆一, 内川誠, 高橋遥一郎, 佐野利恵, 中島たみ子,小湊慶彦.
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] A遺伝子イントロン1の転写制御領域に23bpの欠失がみられた日本人Am型の2例. (2014)
  • Author(s): 増田英敏, 常山初江, 伊佐和美, 小笠原健一, 矢部隆一, 内川誠, 南隆彦, 高橋遥一郎, 佐野利恵, 中島たみ子,小湊慶彦.
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] ABO遺伝子血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子, 藤原純子, 竹下治男, 安田年博, 小湊慶彦, 岸田哲子.
  • Organizer: DNA多型学会第22回学術集会
  • Place of Presentation: 仙台市戦災復興記念館（仙台）
• [Presentation] ABO遺伝子血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子, 竹下治男, 安田年博, 小湊慶彦.
  • Organizer: 第97次日本法医学会学術全国集会
  • Place of Presentation: ロイトン札幌（札幌）