Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC]

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. Our overall design it to compare between Smchd1 control and Smchd1 maternally deleted samples. We have performed RNA-seq in a differentiation timecourse in 4 replicate mESC of each genotype with 6 timepoints (timepoints are missing for three samples across two replicate differentiation experiments; wt day 1 line 1 rep 3, mat del DME LIF line 2 rep 4, mat del day 2.5 line 2 rep 4), comparing the Smchd1 maternally deleted to the control, at the matched timepoint.