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

Ho, B., Greenlaw, K., Al Tuwaijri, A., Moussette, S., Martinez, F., Giorgio, E., et al. (2018). 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, 9(1): 9:10. doi:10.1186/s13293-018-0169-7.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-CEAE-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-CEAF-4
Genre: Journal Article

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HO.pdf (Publisher version), 833KB
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© The Author(s). 2018

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 Creators:
Ho, B., Author
Greenlaw, K., Author
Al Tuwaijri, A., Author
Moussette, S., Author
Martinez, F., Author
Giorgio, E., Author
Brusco, A., Author
Ferrero, G. B., Author
Linhares, N. D., Author
Valadares, E. R., Author
Svartman, M., Author
Kalscheuer, V. M.1, Author              
Rodriguez Criado, G., Author
Laprise, C., Author
Greenwood, C. M. T., Author
Naumova, A. K., Author
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385702              

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Free keywords: DNA methylation; Sex; X chromosome; Y chromosome
 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.

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Language(s): eng - English
 Dates: 2018-01-312018-02-20
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1186/s13293-018-0169-7
ISSN: 2042-6410 (Electronic)
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Title: Biology of Sex Differences
  Alternative Title : Biology of sex differences
Source Genre: Journal
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Publ. Info: London : BioMed Central
Pages: - Volume / Issue: 9 (1) Sequence Number: 9:10 Start / End Page: - Identifier: -