Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures

Hidehito Inagaki, Sayuri Ota, Haruki Nishizawa, Hironori Miyamura, Kumiko Nakahira, Machiko Suzuki, Sachie Nishiyama, Takema Kato, Itaru Yanagihara, Hiroki Kurahashi

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Recent findings have highlighted the possibility that polymorphisms within the annexin A5 gene (ANXA5) promoter contribute to the etiology of various obstetric complications. However, the underlying mechanisms are unknown. The M2 haplotype of the ANXA5 shows lower activity and less expression of ANXA5 mRNA. This gene promoter region has a motif that potentially forms a G-quadruplex structure. In vitro G-quadruplex propensity estimated by circular dichroism indicated that the M2 haplotype oligonucleotide manifested a decreased potential for G-quadruplex formation. In addition, in vivo G-quadruplex formation of the promoter region was evidenced by the presence of single-stranded DNA shown by sodium bisulfite treatment of placental genomic DNA. Comparative analysis indicated less potential in the M2 allele than the major allele. Promoter activity of the two haplotypes determined by luciferase reporter analysis correlated with the estimated G-quadruplex propensity. Our data lend support to the developing paradigm that genomic variation affects gene expression levels via DNA secondary structures leading to the disease susceptibility.

本文言語English
ページ(範囲)459-466
ページ数8
ジャーナルJournal of Human Genetics
64
5
DOI
出版ステータスPublished - 01-05-2019

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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