X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

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

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. More... »

PAGES

10

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13293-018-0169-7

DOI

http://dx.doi.org/10.1186/s13293-018-0169-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101140323

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29463315


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442 schema:name Ambulatório de Erros Inatos do Metabolismo, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
443 Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
444 Setor de Citogenética, Laboratório Central do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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447 schema:name The Research Institute of the McGill University Health Centre (MUHC), 1001 Decarie Blvd., Bloc E, Room EM03226, H4A 3J1, Montreal, Quebec, Canada
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450 schema:name Department of Medical Sciences, University of Torino, 10126, Turin, Italy
451 Department of Public Health and Pediatrics, University of Torino, 10126, Turin, Italy
452 Medical Genetics Unit, Città della Salute e della Scienza University Hospital, 10126, Turin, Italy
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455 schema:name Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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457 https://www.grid.ac/institutes/grid.84393.35 schema:alternateName Hospital Universitari i Politècnic La Fe
458 schema:name Unidad de Genética, Hospital Universitario y Politécnico La Fe, 46026, Valencia, Spain
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