A locus in mice known as strain-specific modifier 1 (Ssm1) has previously been shown to be responsible for the strain-dependent methylation of E. coli gpt-containing transgenic sequences. Now, Ursula Storb and co-workers identify the Ssm1b gene that underlies this phenotype and characterise its expression in early mouse embryos (p. 2024). Through extensive mapping studies, the researchers identify Ssm1b as a KRAB-zinc finger gene that is located on distal chromosome 4. They further demonstrate that Ssm1b is expressed in early embryos up until embryonic day 8.5 and, in line with this, its target transgene gains partial methylation by this stage. The Ssm1b gene lacks the conserved transferase sequence present in all DNA methyltransferases, but the researchers demonstrate that Ssm1b mediates transgene methylation via the de novo methyltransferase Dnmt3b. By contrast, they report, the methylated DNA-binding protein Mecp2 is not involved in Ssm1b-dependent DNA methylation. These findings, together with preliminary analyses of Ssm1b function, uncover a novel gene and highlight the existence of a new family of genes that can initiate DNA methylation and chromatin modification and hence are likely to be involved in the epigenetic control of early development.