Article

Sperm Methylation Profiles Reveal Features of Epigenetic Inheritance and Evolution in Primates

Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Cell (Impact Factor: 32.24). 09/2011; 146(6):1029-41. DOI: 10.1016/j.cell.2011.08.016
Source: PubMed

ABSTRACT

During germ cell and preimplantation development, mammalian cells undergo nearly complete reprogramming of DNA methylation patterns. We profiled the methylomes of human and chimp sperm as a basis for comparison to methylation patterns of ESCs. Although the majority of promoters escape methylation in both ESCs and sperm, the corresponding hypomethylated regions show substantial structural differences. Repeat elements are heavily methylated in both germ and somatic cells; however, retrotransposons from several subfamilies evade methylation more effectively during male germ cell development, whereas other subfamilies show the opposite trend. Comparing methylomes of human and chimp sperm revealed a subset of differentially methylated promoters and strikingly divergent methylation in retrotransposon subfamilies, with an evolutionary impact that is apparent in the underlying genomic sequence. Thus, the features that determine DNA methylation patterns differ between male germ cells and somatic cells, and elements of these features have diverged between humans and chimpanzees.

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    • "HMRs were identified as previously described[22]. Briefly, the raw methylated and unmethylated read counts of each CpG site, modeled with a beta-binomial distribution, provided the input for a hidden Markov segmentation model with two states (high and low methylation). "
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    • "To increase the fraction of the epigenetic coverage, we also included an analysis of the methylation level of Sata, is largely confined to chromosome centromeres, whereas LINE-1 and Alu are interspersed throughout the genome. In contrast to the similarity of transposable sequence percent methylation in somatic and germ cells, Sata methylation level appeared to be lower in sperm than in PBLsFabris et al., 2011], confirming previous reports[Weisenberger et al., 2005;Yamagata et al., 2007;Molaro et al., 2011]. An association has been proposed between the hypomethylation of pericentromeric DNA in germ cells and a germline specific architecture of the centromere influencing gene expression and/or chromosome segregation in meio- sis[Yamagata et al., 2007]. "
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    • "The normal sperm epigenome has been described in detail (Hammoud et al. 2009, 2014; Molaro et al. 2011) and contains important features. First, similar to the stem cell epigenome, the promoter regions of both bivalently and monovalently marked developmental genes in sperm are hypomethylated compared to somatic cells (Molaro et al. 2011). These observations further support the hypothesis of a poised sperm epigenome , transcriptionally silenced, but 'poised' to facilitate rapid initiation of transcription, an observation confirmed in the zebrafish (Wu et al. 2011). "
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