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Imprinted genes are important in development and their allelic expression is mediated by imprinting control regions (ICRs). On their DNA‐methylated allele, ICRs are marked by trimethylation at H3 Lys 9 (H3K9me3) and H4 Lys 20 (H4K20me3), similar to pericentric heterochromatin. Here, we investigate which histone methyltransferases control this methylation of histone at ICRs. We found that inactivation of SUV4‐20H leads to the loss of H4K20me3 and increased levels of its substrate, H4K20me1. H4K20me1 is controlled by PR‐SET7 and is detected on both parental alleles. The disruption of SUV4‐20H or PR‐SET7 does not affect methylation of DNA at ICRs but influences precipitation of H3K9me3, which is suggestive of a trans‐histone change. Unlike at pericentric heterochromatin, however, H3K9me3 at ICRs does not depend on SUV39H. Our data show not only new similarities but also differences between ICRs and heterochromatin, both of which show constitutive maintenance of methylation of DNA in somatic cells.

PR‐SET7 and SUV4‐20H regulate H4 lysine‐20 methylation at imprinting control regions in the mouse