GSE203617
Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [ESC RRBS]
Parents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect on Hox gene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation of Hox genes post-implantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo. Hox genes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not deplete these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriate Hox gene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype. Overall design: Our overall design it to compare between Smchd1 control and Smchd1 maternally deleted samples. We have performed reduced representation bisulfite sequqencing (RRBS) in a differentiation timecourse in 2 replicate mESC of each genotype at 2 timepoints comparing the Smchd1 maternally deleted to the control, at the matched timepoint.