Evolution of X-chromosome inactivation and embryogenesis in mammals
In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY) during a process known as X-chromosome inactivation. The strategy to achieve it varies between the two infraclasses of mammals: eutherians (placentalia) and metatherians (marsupialia).
X-inactivation in eutherian mammals is mediated by the non-coding RNA XIST, which coats the future-inactive X chromosome and induces chromatin changes that cause gene silencing. Metatherian mammals, which diverged from eutherians 160 million years ago, do not have an XIST gene and the process of X-inactivation evolved convergently. To understand how X-inactivation is achieved in metatherians and get a bigger picture of the importance of this process, we use the grey short-tailed opossum Monodelphis domestica as a model organism.
We discovered RSX (RNA-on-the-silent X) and its antisense partner XSR, two metatherian non-coding RNAs with a role in X-inactivation. Several projects in the lab are focused on understanding the functions of RSX and XSR, the key molecular aspects of embryonic development in the opossum, how X-inactivation is established in the embryo and how it is maintained in adult tissues. X-inactivation in metatherians is imprinted in the germline and, as a result, the paternal X chromosome is always silenced. One of our objectives is to elucidate the epigenetic mechanism that is responsible for the establishment and maintenance of imprinted X-inactivation. Chromatin architecture is known to play an important role in gene regulation and in X-inactivation in particular in eutherians. Another aim is therefore to understand how the genome is organised in 3D in the opossum.
Overall, our aim is to provide insight into the evolution of X-dosage compensation mechanisms in mammals.