<b><i>CBX2</i></b> in DSD: The Quirky Kid on the Block

Abstract

Sex development is an intricate and crucial process in all vertebrates that ensures the continued propagation of genetic diversity within a species, and ultimately their survival. Perturbations in this process can manifest as disorders/differences of sex development (DSD). Various transcriptional networks have been linked to development of the gonad into either male or female, which is actively driven by a set of genes that function in a juxtaposed manner and is maintained through the developmental stages to preserve the final sexual identity. One such identified gene is Chromobox homolog 2 (<i>CBX2</i>), an important ortholog of the Polycomb group (PcG) proteins, that functions as both chromatin modifier and highly dynamic transactivator. <i>CBX2</i> was shown to be an essential factor for gonadal development in mammals, as genetic variants or loss-of-function of <i>CBX2</i> can cause sex reversal in mice and humans. Here we will provide an overview of <i>CBX2</i>, its biological functions at molecular level, and the CBX2-dependent transcriptional landscape in gonadal development and DSD.