X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells
Abstract Background Sexual dimorphism in DNA methylation levels is a recurrent epigenetic feature in different human cell types and has been implicated in predisposition to disease, such as psychiatric and autoimmune disorders. To elucidate the genetic origins of sex-specific DNA methylation, we exa...
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doaj-39fc1babb93840e59dac6f833b1dbabe2020-11-24T22:06:47ZengBMCBiology of Sex Differences2042-64102018-02-019111010.1186/s13293-018-0169-7X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cellsBianca Ho0Keelin Greenlaw1Abeer Al Tuwaijri2Sanny Moussette3Francisco Martínez4Elisa Giorgio5Alfredo Brusco6Giovanni Battista Ferrero7Natália D. Linhares8Eugênia R. Valadares9Marta Svartman10Vera M. Kalscheuer11Germán Rodríguez Criado12Catherine Laprise13Celia M. T. Greenwood14Anna K. Naumova15Department of Human Genetics, McGill UniversityLady Davis Research InstituteDepartment of Human Genetics, McGill UniversityThe Research Institute of the McGill University Health Centre (MUHC)Unidad de Genética, Hospital Universitario y Politécnico La FeDepartment of Medical Sciences, University of TorinoDepartment of Medical Sciences, University of TorinoDepartment of Public Health and Pediatrics, University of TorinoSetor de Citogenética, Laboratório Central do Hospital das Clínicas da Universidade Federal de Minas GeraisDepartamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas GeraisDepartamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas GeraisResearch Group Development and Disease, Max Planck Institute for Molecular GeneticsUnidad de Genética Clínica, Hospital Virgen del RocíoDépartement des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, Centre intégré universitaire de santé et services sociaux du SaguenayDepartment of Human Genetics, McGill UniversityDepartment of Human Genetics, McGill UniversityAbstract Background Sexual dimorphism in DNA methylation levels is a recurrent epigenetic feature in different human cell types and has been implicated in predisposition to disease, such as psychiatric and autoimmune disorders. To elucidate the genetic origins of sex-specific DNA methylation, we examined DNA methylation levels in fibroblast cell lines and blood cells from individuals with different combinations of sex chromosome complements and sex phenotypes focusing on a single autosomal region––the differentially methylated region (DMR) in the promoter of the zona pellucida binding protein 2 (ZPBP2) as a reporter. Results Our data show that the presence of the sex determining region Y (SRY) was associated with lower methylation levels, whereas higher X chromosome dosage in the absence of SRY led to an increase in DNA methylation levels at the ZPBP2 DMR. We mapped the X-linked modifier of DNA methylation to the long arm of chromosome X (Xq13-q21) and tested the impact of mutations in the ATRX and RLIM genes, located in this region, on methylation levels. Neither ATRX nor RLIM mutations influenced ZPBP2 methylation in female carriers. Conclusions We conclude that sex-specific methylation differences at the autosomal locus result from interaction between a Y-linked factor SRY and at least one X-linked factor that acts in a dose-dependent manner.http://link.springer.com/article/10.1186/s13293-018-0169-7DNA methylationSexX chromosomeY chromosome |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bianca Ho Keelin Greenlaw Abeer Al Tuwaijri Sanny Moussette Francisco Martínez Elisa Giorgio Alfredo Brusco Giovanni Battista Ferrero Natália D. Linhares Eugênia R. Valadares Marta Svartman Vera M. Kalscheuer Germán Rodríguez Criado Catherine Laprise Celia M. T. Greenwood Anna K. Naumova |
spellingShingle |
Bianca Ho Keelin Greenlaw Abeer Al Tuwaijri Sanny Moussette Francisco Martínez Elisa Giorgio Alfredo Brusco Giovanni Battista Ferrero Natália D. Linhares Eugênia R. Valadares Marta Svartman Vera M. Kalscheuer Germán Rodríguez Criado Catherine Laprise Celia M. T. Greenwood Anna K. Naumova X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells Biology of Sex Differences DNA methylation Sex X chromosome Y chromosome |
author_facet |
Bianca Ho Keelin Greenlaw Abeer Al Tuwaijri Sanny Moussette Francisco Martínez Elisa Giorgio Alfredo Brusco Giovanni Battista Ferrero Natália D. Linhares Eugênia R. Valadares Marta Svartman Vera M. Kalscheuer Germán Rodríguez Criado Catherine Laprise Celia M. T. Greenwood Anna K. Naumova |
author_sort |
Bianca Ho |
title |
X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells |
title_short |
X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells |
title_full |
X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells |
title_fullStr |
X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells |
title_full_unstemmed |
X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells |
title_sort |
x chromosome dosage and presence of sry shape sex-specific differences in dna methylation at an autosomal region in human cells |
publisher |
BMC |
series |
Biology of Sex Differences |
issn |
2042-6410 |
publishDate |
2018-02-01 |
description |
Abstract Background Sexual dimorphism in DNA methylation levels is a recurrent epigenetic feature in different human cell types and has been implicated in predisposition to disease, such as psychiatric and autoimmune disorders. To elucidate the genetic origins of sex-specific DNA methylation, we examined DNA methylation levels in fibroblast cell lines and blood cells from individuals with different combinations of sex chromosome complements and sex phenotypes focusing on a single autosomal region––the differentially methylated region (DMR) in the promoter of the zona pellucida binding protein 2 (ZPBP2) as a reporter. Results Our data show that the presence of the sex determining region Y (SRY) was associated with lower methylation levels, whereas higher X chromosome dosage in the absence of SRY led to an increase in DNA methylation levels at the ZPBP2 DMR. We mapped the X-linked modifier of DNA methylation to the long arm of chromosome X (Xq13-q21) and tested the impact of mutations in the ATRX and RLIM genes, located in this region, on methylation levels. Neither ATRX nor RLIM mutations influenced ZPBP2 methylation in female carriers. Conclusions We conclude that sex-specific methylation differences at the autosomal locus result from interaction between a Y-linked factor SRY and at least one X-linked factor that acts in a dose-dependent manner. |
topic |
DNA methylation Sex X chromosome Y chromosome |
url |
http://link.springer.com/article/10.1186/s13293-018-0169-7 |
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