Smchd1 is a maternal effect gene required for autosomal imprinting

Genomic imprinting establishes allele-biased expression of a suite of mammalian genes based on their parent of origin. Imprinted expression is achieved via parent-of-origin specific epigenetic marks under the control of maternal effect proteins supplied in the oocyte. Here we report Structural maintenance of chromosomes hinge domain containing 1 (Smchd1) as a novel maternal effect gene that regulates the imprinting of 16 genes. The majority of these genes only show loss of imprinting post-implantation, indicating maternal Smchd1 imparts a long-lived epigenetic effect. Smchd1-sensitive genes include both those controlled by germline polycomb marks and by germline DNA methylation imprints. In contrast to other known maternal effect genes affecting the latter set of genes, maternal Smchd1 does not affect germline DNA methylation imprints. Smchd1-sensitive genes are united by their reliance on polycomb-mediated histone methylation as germline or secondary imprints, suggesting Smchd1 acts downstream of polycomb imprints to mediate its function. We propose that Smchd1 translates these imprints to establish a heritable chromatin state required for imprinted expression later in development. We have shown Smchd1 is a novel maternal effect gene required for imprinted expression that operates via a new mechanism for maternal effect genes.