Transcription and histone methylation changes correlate with imprint acquisition in male germ cells

Genomic imprinting in mammals is controlled by DNA methylation imprints that are acquired in the gametes, at essential sequence elements called ‘imprinting control regions ’ (ICRs). What signals paternal imprint acquisition in male germ cells remains unknown. To address this question, we explored histone methylation at ICRs in mouse primordial germ cells (PGCs). By 13.5 days post coitum (d.p.c.), H3 lysine-9 and H4 lysine-20 trimethyla-tion are depleted from ICRs in male (and female) PGCs, indicating that these modifications do not signal subse-quent imprint acquisition, which initiates at B15.5 d.p.c. Furthermore, during male PGC development, H3 lysine-4 trimethylation becomes biallelically enriched at ‘maternal’ ICRs, which are protected against DNA methylation, and whose promoters are active in the male germ cells. Remarkably, high transcriptional read-through is detected at the paternal ICRs H19-DMR and Ig-DMR at the time of imprint establishment, from one of the strands predomi-nantly. Combined, our data evoke a model in which differential histone modification states linked to transcrip-tional events may signal the specificity of imprint acquisi-tion during spermatogenesis