Methylation status of genes escaping from X-chromosome inactivation in patients with X-chromosome rearrangements

被引：5

作者：

Kawashima, Sayaka ^{[1
,2
]}

Hattori, Atsushi ^{[1
]}

Suzuki, Erina ^{[1
]}

Matsubara, Keiko ^{[1
]}

Toki, Machiko ^{[3
,4
]}

Kosaki, Rika ^{[5
]}

Hasegawa, Yukihiro ^{[6
]}

Nakabayashi, Kazuhiko ^{[7
]}

Fukami, Maki ^{[1
]}

Kagami, Masayo ^{[1
]}

机构：

[1] Natl Res Inst Child Hlth & Dev, Dept Mol Endocrinol, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535, Japan

[2] Toho Univ, Sch Med, Dept Pediat, Aoba Ku, 1-1 Seiry Omachi, Sendai, Miyagi 9808574, Japan

[3] Hiratsuka City Hosp, Dept Pediat, 1-19-1 Minamihara, Hiratsuka, Kanagawa 2540065, Japan

[4] Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[5] Natl Ctr Child Hlth & Dev, Div Med Genet, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535, Japan

[6] Tokyo Metropolitan Childrens Med Ctr, Div Endocrinol & Metab, 2-8-29 Musashidai, Fuchu, Tokyo 1838561, Japan

[7] Natl Res Inst Child Hlth & Dev, Dept Maternal Fetal Biol, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535, Japan

来源：

CLINICAL EPIGENETICS | 2021年 / 13卷 / 01期

基金：

日本学术振兴会;

关键词：

X-chromosome inactivation; Escape gene; X-chromosome rearrangement; EXPRESSION; FEATURES; ELEMENTS;

D O I：

10.1186/s13148-021-01121-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundX-chromosome inactivation (XCI) is a mechanism in which one of two X chromosomes in females is randomly inactivated in order to compensate for imbalance of gene dosage between sexes. However, about 15% of genes on the inactivated X chromosome (Xi) escape from XCI. The methylation level of the promoter region of the escape gene is lower than that of the inactivated genes. Dxz4 and/or Firre have critical roles for forming the three-dimensional (3D) structure of Xi. In mice, disrupting the 3D structure of Xi by deleting both Dxz4 and Firre genes led to changing of the escape genes list. To estimate the impact for escape genes by X-chromosome rearrangements, including DXZ4 and FIRRE, we examined the methylation status of escape gene promoters in patients with various X-chromosome rearrangements.ResultsTo detect the breakpoints, we first performed array-based comparative genomic hybridization and whole-genome sequencing in four patients with X-chromosome rearrangements. Subsequently, we conducted array-based methylation analysis and reduced representation bisulfite sequencing in the four patients with X-chromosome rearrangements and controls. Of genes reported as escape genes by gene expression analysis using human hybrid cells in a previous study, 32 genes showed hypomethylation of the promoter region in both male controls and female controls. Three patients with X-chromosome rearrangements had no escape genes with abnormal methylation of the promoter region. One of four patients with the most complicated rearrangements exhibited abnormal methylation in three escape genes. Furthermore, in the patient with the deletion of the FIRRE gene and the duplication of DXZ4, most escape genes remained hypomethylated.ConclusionX-chromosome rearrangements are unlikely to affect the methylation status of the promoter regions of escape genes, except for a specific case with highly complex rearrangements, including the deletion of the FIRRE gene and the duplication of DXZ4.

引用

页数：11

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