Smchd1 is a maternal effect gene required for genomic imprinting (original) (raw)
Genomic imprinting establishes parental allele-biased expression of a suite of mammalian genes based on parent-of-origin specific epigenetic marks. These marks are under the control of maternal effect proteins supplied in the oocyte. Here we report epigenetic repressor Smchd1 as a novel maternal effect gene that regulates the imprinted expression of ten genes in mice. We also found zygotic SMCHD1 had a dose-dependent effect on the imprinted expression of seven genes. Together, zygotic and maternal SMCHD1 regulate three classic imprinted clusters and eight other genes, including non-canonical imprinted genes. Interestingly, the loss of maternal SMCHD1 does not alter germline DNA methylation imprints pre-implantation or later in gestation. Instead, what appears to unite most imprinted genes sensitive to SMCHD1 is their reliance on polycomb-mediated methylation as germline or secondary imprints, therefore we propose that SMCHD1 acts downstream of polycomb imprints to mediate its function.
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