Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
Sarah A Kinkel
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
Andrés Tapia del Fierro
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
Tamara Beck
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Ellise A Roper
Faculty of Health and Medicine, The University of Newcastle, Newcastle, Australia
Kelsey Breslin
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Jessica Stringer
Monash Biomedicine Discovery institute, Monash University, Clayton, Australia
Monash Biomedicine Discovery institute, Monash University, Clayton, Australia
Heather J Lee
Faculty of Health and Medicine, The University of Newcastle, Newcastle, Australia
Andrew Keniry
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
Matthew E Ritchie
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia; The Department of Mathematics and Statistics, The University of Melbourne, Parkville, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Department of Medical Biology, The University of Melbourne, Parkville, Australia
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.
