Abstract
Uterine leiomyomas are the most common uterine tumors in women. Estrogen receptor-α (ER-α) is more highly expressed in uterine leiomyomas than in normal myometrium, suggesting a link between uterine leiomyomas and ER-α expression. DNA methylation is an epigenetic mechanism of gene regulation and plays important roles in normal embryonic development and in disease progression including cancers. Here, we investigated the DNA methylation status of the ER-α promoter region (-1188 to +229 bp) in myometrium and leiomyoma. By sodium bisulfite sequencing, 49 CpG sites in the proximal promoter region of ER-α gene were shown to be unmethylated in both leiomyoma and normal myometrium. At seven CpG sites in the distal promoter region of the ER-α gene, there was a variation in DNA methylation status in myometrium and leiomyoma. Further analysis of the DNA methylation status by bisulfite restriction mapping among 11 paired samples of myometrium and leiomyoma indicated that CpG sites in the distal region of ER-α promoter are hypomethylated in leiomyomas of nine patients. In those patients, ER-α mRNA levels tended to be higher in the leiomyoma than in the myometrium. In conclusion, there was an aberrant DNA methylation status in the promoter region of ER-α gene in uterine leiomyoma, which may be associated with high ER-α mRNA expression.
| Original language | English |
|---|---|
| Pages (from-to) | 539-545 |
| Number of pages | 7 |
| Journal | Molecular Human Reproduction |
| Volume | 14 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2008 |
| Externally published | Yes |
Fingerprint
Keywords
- DNA methylation
- Epigenetics
- ER-α promoter
- Estrogen receptor-α
- Leiomyoma
ASJC Scopus subject areas
- Molecular Biology
- Embryology
- Cell Biology
- Genetics
- Developmental Biology
- Reproductive Medicine
- Obstetrics and Gynaecology
Cite this
Potential link between estrogen receptor-α gene hypomethylation and uterine fibroid formation. / Asada, Hiromi; Yamagata, Yoshiaki; Taketani, Toshiaki; Matsuoka, Aki; Tamura, Hiroshi; Hattori, Naoko; Ohgane, Jun; Hattori, Naka; Shiota, Kunio; Sugino, Norihiro.
In: Molecular Human Reproduction, Vol. 14, No. 9, 2008, p. 539-545.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potential link between estrogen receptor-α gene hypomethylation and uterine fibroid formation
AU - Asada, Hiromi
AU - Yamagata, Yoshiaki
AU - Taketani, Toshiaki
AU - Matsuoka, Aki
AU - Tamura, Hiroshi
AU - Hattori, Naoko
AU - Ohgane, Jun
AU - Hattori, Naka
AU - Shiota, Kunio
AU - Sugino, Norihiro
PY - 2008
Y1 - 2008
N2 - Uterine leiomyomas are the most common uterine tumors in women. Estrogen receptor-α (ER-α) is more highly expressed in uterine leiomyomas than in normal myometrium, suggesting a link between uterine leiomyomas and ER-α expression. DNA methylation is an epigenetic mechanism of gene regulation and plays important roles in normal embryonic development and in disease progression including cancers. Here, we investigated the DNA methylation status of the ER-α promoter region (-1188 to +229 bp) in myometrium and leiomyoma. By sodium bisulfite sequencing, 49 CpG sites in the proximal promoter region of ER-α gene were shown to be unmethylated in both leiomyoma and normal myometrium. At seven CpG sites in the distal promoter region of the ER-α gene, there was a variation in DNA methylation status in myometrium and leiomyoma. Further analysis of the DNA methylation status by bisulfite restriction mapping among 11 paired samples of myometrium and leiomyoma indicated that CpG sites in the distal region of ER-α promoter are hypomethylated in leiomyomas of nine patients. In those patients, ER-α mRNA levels tended to be higher in the leiomyoma than in the myometrium. In conclusion, there was an aberrant DNA methylation status in the promoter region of ER-α gene in uterine leiomyoma, which may be associated with high ER-α mRNA expression.
AB - Uterine leiomyomas are the most common uterine tumors in women. Estrogen receptor-α (ER-α) is more highly expressed in uterine leiomyomas than in normal myometrium, suggesting a link between uterine leiomyomas and ER-α expression. DNA methylation is an epigenetic mechanism of gene regulation and plays important roles in normal embryonic development and in disease progression including cancers. Here, we investigated the DNA methylation status of the ER-α promoter region (-1188 to +229 bp) in myometrium and leiomyoma. By sodium bisulfite sequencing, 49 CpG sites in the proximal promoter region of ER-α gene were shown to be unmethylated in both leiomyoma and normal myometrium. At seven CpG sites in the distal promoter region of the ER-α gene, there was a variation in DNA methylation status in myometrium and leiomyoma. Further analysis of the DNA methylation status by bisulfite restriction mapping among 11 paired samples of myometrium and leiomyoma indicated that CpG sites in the distal region of ER-α promoter are hypomethylated in leiomyomas of nine patients. In those patients, ER-α mRNA levels tended to be higher in the leiomyoma than in the myometrium. In conclusion, there was an aberrant DNA methylation status in the promoter region of ER-α gene in uterine leiomyoma, which may be associated with high ER-α mRNA expression.
KW - DNA methylation
KW - Epigenetics
KW - ER-α promoter
KW - Estrogen receptor-α
KW - Leiomyoma
UR - http://www.scopus.com/inward/record.url?scp=53049107302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53049107302&partnerID=8YFLogxK
U2 - 10.1093/molehr/gan045
DO - 10.1093/molehr/gan045
M3 - Article
C2 - 18701604
AN - SCOPUS:53049107302
VL - 14
SP - 539
EP - 545
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
SN - 1360-9947
IS - 9
ER -