A tale of two fates: the role of histone modifications in establishing bipotentiality

Sex determination and differentiation is an essential process all mammals must undergo to reproduce. This process in mammals is initiated through the development of a bipotential tissue, the urogenital ridge (UGR), which differentiates into two morphologically different tissues; testes in male and ovaries in females. This is a genetically controlled process with the presence or absence of the Sry gene determining the sexual fate of an embryo. Many genetic pathways have been implicated in the development of the bipotential UGR but the epigenetic regulatory mechanisms involved are relatively unknown. Previously, to obtain a global view of genes active or actively repressed in the mouse UGR at E11.5, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) had been performed for active (H3K4me3) and repressive (H3K27me3) histone modifications. Analysis showed overrepresentation of genes linked to the Wnt signaling pathway targeted for epigenetic regulation from both histone modification data sets (Yang and Wilson, unpublished). Thus, we aimed to investigate the role of epigenetic mechanisms to histone proteins in the UGR prior to differentiation into a testis or ovary, on a set of targets involved in the Wnt signaling pathway. Four enrichment areas were chosen for ChIP-seq validation, Wnt10, Fzd6, Wnt4 and Fzd8. Significant enrichment for Wnt10a in association with H3K4me3 modifications and Wnt10a and Fzd6 in association with H3K27me3 modifications was observed through ChIP-qPCR (p