Potential Mechanisms of Aberrant DNA Hypomethylation on the X Chromosome in Uterine Leiomyomas
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概要
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We recently found that aberrant DNA hypomethylation is more common on the X chromosome than on other chromosomes in uterine leiomyomas by genome-wide DNA methylation profiling. To investigate the mechanism of aberrant hypomethylation on the X chromosome in uterine leiomyomas, we analyzed methylome and transcriptome data from three cases of leiomyomas and the adjacent myometrium. We found that eleven of the aberrantly hypomethylated genes on the X chromosome were common to the three cases. None of these 11 genes were transcriptionally upregulated in the leiomyoma. However, one of them, TSPYL2, was hypomethylated in 68% of multiple leiomyoma specimens. The incidence of aberrant hypomethylation of TSPYL2 was comparable to that of the MED12 mutation (68%), which is known to be detected at a high frequency in uterine leiomyomas. We also analyzed the aberration of the X chromosome inactivation (XCI) mechanism in uterine leiomyomas. Hypomethylation was not enriched in the imprinted genes, suggesting that dysfunction of polycomb repressive complexes is not involved in the aberrant hypomethylation on the X chromosome. The expression analysis of XCI-related genes revealed that the XIST and SATB1 expression was downregulated in 36% and 46% of 11 leiomyoma specimens, respectively, while the HNRNPU and SMCHD1 expression was not altered. In conclusion, the aberration of XCI-related genes such as SATB1 or XIST may be involved in aberrant hypomethylation on the X chromosome in a certain population of the patients with uterine leiomyomas. TSPYL2 of the aberrantly hypomethylated genes on the X chromosome can be used as a biomarker of uterine leiomyomas.
- 日本繁殖生物学会の論文
著者
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Tamura Isao
Department of Biochemistry Osaka Dental University
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Yamagata Yoshiaki
Department Of Obstetrics And Gynecology Yamaguchi University Graduate School Of Medicine
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Maekawa Ryo
Department Of Biological And Environmental Chemistry Kitami Institute Of Technology
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Asada Hiromi
Department Of Obstetrics And Gynecology Yamaguchi University Graduate School Of Medicine
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Sugino Norihiro
Department Of Obstetrics And Gynecology Graduate School Of Medicine Yamaguchi University
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Tamura Hiroshi
Department Of Agricultural Chemistry Faculty Of Agriculture Niigata University
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Okada Maki
Department Of Neurosurgery Shinshu University School Of Medicine
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Sato Shun
Department Of Innovative And Engineered Materials Tokyo Institute Of Technology
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YAMAGATA Yoshiaki
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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LEE Lifa
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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SATO Shun
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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SUGINO Norihiro
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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OKADA Maki
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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TAMURA Isao
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
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