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


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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    • "To gain insights across the entire human germline cycle, we included published BS-seq data of human sperm and ICM (Guo et al., 2014; Molaro et al., 2011). As a result of de novo methylation, sperm dramatically gained methylation to 87% from $4% in Wk9 male hPGCs (Figures 4A and 4C). "
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    • "Cells in these compartments have previously been observed to segregate similarly based upon expression patterns (Charafe-Jauffret et al., 2006; dos Santos et al., 2013) As with other somatic cell types analyzed to date, mammary methylomes exhibit discrete intervals of hypomethylation, punctuating the globally high background methylation. Using a previously described method (Hodges et al., 2011; Molaro et al., 2011; Schlesinger et al., 2013), we identified the set of hypomethylated regions (HMRs) in each methylome. HMRs correspond to regions with low methylation in the underlying population of cells and are a suitable basis for globally describing epigenetic alterations associated with mammary development. "
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