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Whole-genome sequencing of H3K4me3 and DNA methylation in human sperm reveals regions of overlap linked to fertility and development
The paternal environment has been linked to infertility and negative outcomes. Such effects may be transmitted via sperm through histone modifications. To date, in-depth profiling of the sperm chromatin in men has been limited. Here, we use deep sequencing to characterize the sperm profiles of histo...
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Published in: | Cell reports (Cambridge) 2021-07, Vol.36 (3), p.109418-109418, Article 109418 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
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Online Access: | Get full text |
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Summary: | The paternal environment has been linked to infertility and negative outcomes. Such effects may be transmitted via sperm through histone modifications. To date, in-depth profiling of the sperm chromatin in men has been limited. Here, we use deep sequencing to characterize the sperm profiles of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA methylation in a representative reference population of 37 men. Our analysis reveals that H3K4me3 is localized throughout the genome and at genes for fertility and development. Remarkably, enrichment is also found at regions that escape epigenetic reprogramming in primordial germ cells, embryonic enhancers, and short-interspersed nuclear elements (SINEs). There is significant overlap in H3K4me3 and DNA methylation throughout the genome, suggesting a potential interplay between these marks previously reported to be mutually exclusive in sperm. Comparisons made between H3K4me3 marked regions in sperm and the embryonic transcriptome suggest an influence of paternal chromatin on embryonic gene expression.
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•Deep sequencing identifies regions bearing H3K4me3 in human sperm•H3K4me3 is widely distributed in the genome and is enriched at promoters and SINEs•Sperm H3K4me3 marks developmental genes and correlates with embryonic gene expression•In addition to DNA hypomethylated loci, H3K4me3 also overlaps hypermethylated regions
Lambrot et al. use H3K4me3 ChIP-seq and WGBS to profile the sperm epigenome of Canadian men. Deep sequencing reveals regions enriched for H3K4me3 that overlap with DNA methylation, suggesting a functional relationship in sperm. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2021.109418 |