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Title: Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver.
Austin Authors: AlOgayil, Najla;Bauermeister, Klara;Galvez, Jose Hector;Venkatesh, Varun S ;Zhuang, Qinwei Kim-Wee;Chang, Matthew L;Davey, Rachel A;Zajac, Jeffrey D ;Ida, Kinuyo;Kamiya, Akihide;Taketo, Teruko;Bourque, Guillaume;Naumova, Anna K
Affiliation: Medicine (University of Melbourne)
Department of Biochemistry, McGill University, Montréal, QC, Canada
Department of Human Genetics, McGill University, Montréal, QC, Canada
Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
Canadian Centre for Computational Genomics, Montréal, QC, Canada
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada
The Research Institute of the McGill University Health Centre, Montreal, QC, H4A 1J3, Canada
Department of Surgery, McGill University, Montreal, QC, Canada
Department of Human Genetics, McGill University, Montréal, QC, Canada
Issue Date: 2-Jul-2021
Date: 2021
Publication information: Scientific Reports 2021; 11(1): 13766
Abstract: Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we identified sex-associated differentially methylated regions (sDMRs) that depended on the sex phenotype. Focusing on a panel of validated sex-phenotype dependent male- and female-biased sDMRs, we tested the developmental dynamics of sex bias in liver methylation and the impacts of mutations in the androgen receptor, estrogen receptor alpha, or the transcriptional repressor Bcl6 gene. True hermaphrodites that carry both unilateral ovaries and contralateral testes were also tested. Our data show that sex bias in methylation either coincides with or follows sex bias in the expression of sDMR-proximal genes, suggesting that sex bias in gene expression may be required for demethylation at certain sDMRs. Global ablation of AR, ESR1, or a liver-specific loss of BCL6, all alter sDMR methylation, whereas presence of both an ovary and a testis delays the establishment of male-type methylation levels in hermaphrodites. Moreover, the Bcl6-LKO shows dissociation between expression and methylation, suggesting a distinct role of BCL6 in demethylation of intragenic sDMRs.
DOI: 10.1038/s41598-021-93216-6
Journal: Scientific Reports
PubMed URL: 34215813
Type: Journal Article
Subjects: androgen receptor
estrogen receptor
DNA methylation
Appears in Collections:Journal articles

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