OUP accepted manuscript

Gatev, Evan; Inkster, Amy M.; Konwar, Chaini; Lussier, Alexandre A.; Skakkebæk, Anne; Sokolowski, Marla B.; Gravholt, Claus Højbjerg; Dunn, Erin C.; Kobor, Michæl S.; Aristizabal, Maria J.

doi:10.1093/nar/gkab682

Cited by 18 publications

(1 citation statement)

References 98 publications

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“…2016). Despite this, recent research shows that the adult blood DNA methylome is largely affected by sex, but that these methylome sex differences do not change throughout adulthood and so are largely independent from age effects (72, 73).…”

Section: Discussionmentioning

confidence: 99%

Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

Grant

Wang

Zabet

et al. 2021

Preprint

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Sex differences are known to play a role in disease etiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina EPIC array in human whole blood (n=1171). We identified 554 sex-associated differentially methylated CpG sites (saDMPs) with the majority found to be hypermethylated in females (70%). These saDMP's are enriched in CpG islands and CpG shores and located preferentially at 5'UTRs, 3'UTRs and enhancers. Additionally, we identified 311 significant sex associated differentially methylated regions (saDMRs). Transcription factor binding site enrichment revealed enrichment of transcription factors related to critical developmental processes and sex determination such as SRY and SOX9. Our study reports a reliable catalogue of sex associated CpG sites and elucidates several characteristics of these sites.

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Section: Discussionmentioning

confidence: 99%

Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

Grant

Wang

Zabet

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

The combination of DNA methylome and transcriptome revealed the intergenerational inheritance on the influence of advanced maternal age

Hua

Chen

Meng

et al. 2022

Clinical & Translational Med

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Background The number of women delivering at advanced maternal age (AMA; > = 35) continuously increases in developed and high‐income countries. Large cohort studies have associated AMA with increased risks of various pregnancy complications and adverse pregnancy outcomes, which raises great concerns about the adverse effect of AMA on the long‐term health of offspring. Specific acquired characteristics of parents can be passed on to descendants through certain molecular mechanisms, yet the underlying connection between AMA‐related alterations in parents and that in offspring remains largely uncharted. Methods We profiled the DNA methylomes of paired parental peripheral bloods and cord bloods from 20 nuclear families, including 10 AMA and 10 Young, and additional transcriptomes of 10 paired maternal peripheral bloods and cord bloods. Results We revealed that AMA induced aging‐like changes in DNA methylome and gene expression in both parents and offspring. The expression changes in several genes, such as SLC28A3, were highly relevant to the disorder in DNA methylation. In addition, AMA‐related differentially methylated regions (DMRs) identified in mother and offspring groups showed remarkable similarities in both genomic locations and biological functions, mainly involving neuron differentiation, metabolism, and histone modification pathways. AMA‐related differentially expressed genes (DEGs) shared by mother and offspring groups were highly enriched in the processes of immune cell activation and mitotic nuclear division. We further uncovered developmental‐dependent dynamics for the DNA methylation of intergenerationally correlated DMRs during pre‐implantation embryonic development, as well as diverse gene expression patterns during gametogenesis and early embryonic development for those common AMA‐related DEGs presenting intergenerational correlation, such as CD24. Moreover, some intergenerational DEGs, typified by HTRA3, also showed the same significant alterations in AMA MII oocyte or blastocyst. Conclusions Our results reveal potential intergenerational inheritance of both AMA‐related DNA methylome and transcriptome and provide new insights to understand health problems in AMA offspring.

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Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse

et al. 2022

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Several lines of evidence suggest that the presence of the Y chromosome influences DNA methylation of autosomal loci. To better understand the impact of the Y chromosome on autosomal DNA methylation patterns and its contribution to sex bias in methylation, we identified Y chromosome dependent differentially methylated regions (yDMRs) using whole-genome bisulfite sequencing methylation data from livers of mice with different combinations of sex-chromosome complement and gonadal sex. Nearly 90% of the autosomal yDMRs mapped to transposable elements (TEs) and most of them had lower methylation in XY compared to XX or XO mice. Follow-up analyses of four reporter autosomal yDMRs showed that Y-dependent methylation levels were consistent across most somatic tissues but varied in strains with different origins of the Y chromosome, suggesting that genetic variation in the Y chromosome influenced methylation levels of autosomal regions. Mice lacking the q-arm of the Y chromosome (B6.NPYq-2) as well as mice with a loss-of-function mutation in Kdm5d showed no differences in methylation levels compared to wild type mice. In conclusion, the Y-linked modifier of TE methylation is likely to reside on the short arm of Y chromosome and further studies are required to identify this gene.

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OUP accepted manuscript

Cited by 18 publications

References 98 publications

Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

The combination of DNA methylome and transcriptome revealed the intergenerational inheritance on the influence of advanced maternal age

Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse

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