Simultaneous X-chromosome inactivation and tissue-/cell-type-specific DNA methylation in the transcriptional regulatory region of the X-linked recessive disease gene OTC.
5 affiliations
- 1Graduate School of Agriculture, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, 214-8571, Japan.
- 2Meiji University International Institute for Bio-Resource Research, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, 214-8571, Japan.
- 3Department of Agriculture, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, 214-8571, Japan.
- 4Meiji University International Institute for Bio-Resource Research, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, 214-8571, Japan. [email protected].
- 5Department of Agriculture, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, 214-8571, Japan. [email protected].
Abstract
Background
Variability in disease onset and severity among heterozygous females with X-linked recessive disorders, such as ornithine transcarbamylase (OTC) deficiency, may result from differences in the expression level of the normal allele caused by skewed X-chromosome inactivation (XCI). However, previous studies on the mechanisms of XCI lack relevance to humans. By applying the concept of hypomethylated allele frequency, gene expression can be estimated through DNA methylation analysis of transcriptional regulatory regions, including tissue-/cell-type-specific differentially methylated regions (T-DMRs) and XCI-affected regions.Results
In this study, we identified a porcine OTC transcriptional regulatory region that functions both as a T-DMR and XCI-affected differentially methylated region. Furthermore, by distinguishing alleles using a single nucleotide polymorphism, we detected evidence of skewed XCI in female pigs.Conclusions
Accordingly, by demonstrating that hypomethylated allele frequency reflects the active X allele, this study provides possible molecular evidence of skewed X inactivation through DNA methylation within the OTC T-DMR.
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BibTeX
@article{yamada2026simultaneous,
title = {{Simultaneous X-chromosome inactivation and tissue-/cell-type-specific DNA methylation in the transcriptional regulatory region of the X-linked recessive disease gene OTC.}},
author = {Fuko Yamada and Shiori Hinata and Ryohei Shigeta and Hiroshi Nagashima and Kenji Yamatoya and Jun Ohgane},
journal = {Clinical epigenetics},
year = {2026},
month = jul,
doi = {10.1186/s13148-026-02217-7},
url = {https://europepmc.org/article/MED/42928245},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Simultaneous X-chromosome inactivation and tissue-/cell-type-specific DNA methylation in the transcriptional regulatory region of the X-linked recessive disease gene OTC.
AU - Fuko Yamada
AU - Shiori Hinata
AU - Ryohei Shigeta
AU - Hiroshi Nagashima
AU - Kenji Yamatoya
AU - Jun Ohgane
PY - 2026
DA - 2026/07/29
JO - Clinical epigenetics
DO - 10.1186/s13148-026-02217-7
UR - https://europepmc.org/article/MED/42928245
AB - Background Variability in disease onset and severity among heterozygous females with X-linked recessive disorders, such as ornithine transcarbamylase (OTC) deficiency, may result from differences in the expression level of the normal allele caused by skewed X-chromosome inactivation (XCI). However, previous studies on the mechanisms of XCI lack relevance to humans. By applying the concept of hypomethylated allele frequency, gene expression can be estimated through DNA methylation analysis of transcriptional regulatory regions, including tissue-/cell-type-specific differentially methylated regions (T-DMRs) and XCI-affected regions.Results In this study, we identified a porcine OTC transcriptional regulatory region that functions both as a T-DMR and XCI-affected differentially methylated region. Furthermore, by distinguishing alleles using a single nucleotide polymorphism, we detected evidence of skewed XCI in female pigs.Conclusions Accordingly, by demonstrating that hypomethylated allele frequency reflects the active X allele, this study provides possible molecular evidence of skewed X inactivation through DNA methylation within the OTC T-DMR.
SN - 1868-7083
ER -