Meiotic silencing of unsynapsed chromatin (MSUC) occurs in the germ cells of translocation carriers and may cause meiotic arrest and infertility. We hypothesized that if bypassing meiotic checkpoints MSUC may cause epigenetic defects in sperm. We investigated the meiotic behavior of the Robertsonian translocation Rb (8.12) in mice. The unsynapsed 8 and 12 trivalent was associated with the XY body during early and mid-pachynema in heterozygous Rb (8.12) carriers, suggesting possible silencing of pericentromeric genes, such as the Dnmt3a gene. In wild-type mice, DNMT3A protein showed a dramatic accumulation in the nucleus during the mid-pachytene stage and distinct association with the XY body. In translocation carriers, DNMT3A was less abundant in a proportion of pachytene spermatocytes that also had unsynapsed pericentromeric regions of chromosomes 8 and 12. The same mice had incomplete methylation of the imprinted H19 differentially methylated region (DMR) in sperm. We propose that impaired H19 imprint establishment results from lack of synapsis in chromosomes 8 and 12 probably through transient silencing of a chromosome 8 or 12 gene during pachynema. Furthermore, our findings support the notion that imprint establishment at the H19 locus extends into pachynema.
Mammalian Genome – Springer Journals
Published: Jun 25, 2010
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