Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 459-466 |
| Number of pages | 8 |
| Journal | Journal of Human Genetics |
| Volume | 64 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 01-05-2019 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
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Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures. / Inagaki, Hidehito; Ota, Sayuri; Nishizawa, Haruki; Miyamura, Hironori; Nakahira, Kumiko; Suzuki, Machiko; Nishiyama, Sachie; Kato, Takema; Yanagihara, Itaru; Kurahashi, Hiroki.
In: Journal of Human Genetics, Vol. 64, No. 5, 01.05.2019, p. 459-466.Research output: Contribution to journal › Article
TY - JOUR
T1 - Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures
AU - Inagaki, Hidehito
AU - Ota, Sayuri
AU - Nishizawa, Haruki
AU - Miyamura, Hironori
AU - Nakahira, Kumiko
AU - Suzuki, Machiko
AU - Nishiyama, Sachie
AU - Kato, Takema
AU - Yanagihara, Itaru
AU - Kurahashi, Hiroki
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061965122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061965122&partnerID=8YFLogxK
U2 - 10.1038/s10038-019-0578-4
DO - 10.1038/s10038-019-0578-4
M3 - Article
C2 - 30796324
AN - SCOPUS:85061965122
VL - 64
SP - 459
EP - 466
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 5
ER -