Transcriptional regulation via DNA secondary structure: novel epigenetic mechanism

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670171
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Fujita Health University
• Principal Investigator: KURAHASHI Hiroki 藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: グアニン四重鎖 / DNA二次構造 / プロモーター / アネキシン / 多型 / 習慣流産

Outline of Final Research Achievements

The polymorphisms in the ANXA5 promoter region are associated with recurrent pregnancy loss. The female carriers of M2 haplotype are at high risk of the pregnancy loss. The placenta from the M2 carrier has low level of ANXA5 transcript since the promoter activity of the M2 is low. We identified the consensus sequence for Guanine-quadraplex (G4) formation at this promoter region. We analyzed the potential secondary structure by bisulfite treatment followed by next generation sequencing. The pattern of C-to-T conversion indicated that the polymorphism affected the potential for G4. These data suggest that the low expression levels of ANXA5 via G4 formation induce hypercoagulation leading to high risk of pregnancy loss in M2 carriers.

Free Research Field

臨床遺伝学