Project/Area Number |
13307018
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Legal medicine
|
Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
Principal Investigator |
TAKIZAWA Hisao Toyama Medical and Pharmaceutical University, Faculty of Medicine, Professor, 医学部, 教授 (90171579)
|
Co-Investigator(Kenkyū-buntansha) |
KIMURA Hiroshi Kurume University School of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (20112039)
HATA Yukiko Toyama Medical and Pharmaceutical University, Faculty of Medicine, Assistant, 医学部, 教務職員 (30311674)
KOMINATO Yoshihiko Toyama Medical and Pharmaceutical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30205512)
SOEJIMA Mikiko Kurume University School of Medicine, Faculty of Medicine, Instructor, 医学部, 助手 (80279140)
KODA Yoshiro Kurume University School of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90231307)
|
Project Period (FY) |
2001 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥28,860,000 (Direct Cost: ¥22,200,000、Indirect Cost: ¥6,660,000)
Fiscal Year 2003: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2002: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2001: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
|
Keywords | Blood groups / ABO blood group genes / ABO glycosyltransferases / Fucosyltransferases / Transcription / CpG islands / E box / N box / ABO式血液型 / 遺伝子発現 / 転写制御 / DNAメチレーション / 転写抑制因子 / FUT-2遺伝子 / H遺伝子 / 転写開始点 / プロモーター / 5'RACE法 / DNAメチル化 |
Research Abstract |
Our studies of the transcriptional regulatory mechanism of the human ABO gene indicated that transcription of the ABO gene is regulated by the N box upstream the proximal promoter. N boxes are recognized by bHLH family of transcriptional repressers. Since α 1→2 fucosyltransferases are involved in the synthesis of A and B antigens, the ABO gene is co-expressed with the FUT genes encoding α 1→2 fucosyltransferases. Inspection of the nucleotide sequences of the upstream regions of the human FUT genes revealed E box class A and class B sites which bind bHLH family of transcriptional activators, suggesting that the bHLH family of transcriptional regulators could play crucial roles in expression of those genes. Since transcriptional bHLH repressers can form non-functional heterodimers with other transcriptional bHLH activators, thereby inhibiting the formation of functional heterodimers and repressing transcription, down-regulation of the repressers might relieve the repression of transcription from promoters of the FUT genes. Furthermore, down-regulation of a factor binding with the N box upstream the ABO promoter may relieve the repression, thereby leading to expression of the ABO gene. Therefore, reduction of bHLH family transcription represser may play a role in the co-expression of the FUT and ABO gene which leads to cooperative expression of glycosyltransferases involved in synthesis of A or B antigens.
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