Sexually dimorphic gene expression emerges with embryonic genome activation and is dynamic throughout development (ChIP-seq). Mus musculus

As sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important. To explore this, we generated 72 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation and adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines from which we generated both RNA-seq and multiple ChIP-seq profiles. We complemented this with previously published data to yield 5 snap-shots of pre-implantation development, late-gestation placenta and somatic tissue and multiple adult tissues for integrative analysis. We define a high-confidence sex-dimorphic signature of 56 genes in eight-cell embryos. Sex-chromosome-linked components of this signature are largely conserved throughout pre-implantation development and ES cells, whilst the autosomal component is more dynamic. Sex-biased gene expression is reflected by enrichment for activating and repressive histone modifications. The eight-cell signature is largely non-overlapping with that defined from fetal liver, neither was it correlated with liver or other adult tissues analysed. Fetal and adult liver gene expression signatures are also substantially different, yet a core set of common genes showing modest dimorphic expression was identified. Dramatic sex-specific expression of olfactory receptors was found in fetal liver. Sex-biased expression differences unique to adult liver were enriched for growth hormone-responsiveness. The majority of sex-chromosome based differences identified from eight-cell embryos are also present in placenta but not somatic tissue at the same gestational age. This systematic study identifies three distinct phases of sex dimorphism throughout mouse development, and has significant implications for understanding the developmental origins of sex-specific phenotypes and disease in mammals. Overall design: ChIP seq of Es Cell