Genomic imprinting involves monoallelic expression of a set of genes according to their parent-of-origin. Imprinted expression is enabled by germline DNA or histone methylation imprints that resist reprogramming during preimplantation development. Loss of imprinting due to disruptions can lead to imprinting disorders. It is understood that maternal proteins found in the oocyte are involved in preserving normal imprinted expression by retaining their germline imprints. Despite their importance, only a small number of mammalian maternal effect genes have been identified.
The epigenetic regulator structural maintenance of chromosome hinge domain containing 1 (Smchd1) silences the inactive X chromosome and autosomal genes including imprinted genes at Snrpn and Igf2r cluster. Because of its involvement in imprinted clusters and expression in oocyte we explored its function as a maternal effect gene. We partnered allele-specific genomics with conditional deletion of Smchd1 in the oocyte to test the role of maternally derived Smchd1 in imprinted gene expression. Here we show that Smchd1 is a novel maternal effect gene involved in autosomal imprinting. When Smchd1 is maternally deleted loss of imprinting is observed at 34 imprinted genes including genes at Snrpn, Igf2r and Kcnq1 clusters. Importantly this occurs without alteration to the germline DNA methylation imprints and does not require the imprinted genes to be expressed in the pre-implantation period. These data lead us to propose that Smchd1 operates via a new mechanism for a maternal effect gene, where it establishes an epigenetic memory later required for imprinted expression.