INVESTIGATING THE EPIGENETICS OF X-CHROMOSOME DOSAGE COMPENSATION DURING CELL FATE REPROGRAMMING TO PLURIPOTENCY AND DEVELOPMENT

This research will focus on revealing the mechanisms of a spectacular phenomenon, X-chromosome dosage compensation. In mammals, female cells contain two copies of the X-chromosome, while males only have one copy. To maintain the same amount of active genes as non-sex chromosomes which are present in two copies, the only active X-chromosome in males is upregulated. Moreover, one of the two X-chromosomes in female cells is turned off, and the other is upregulated. Remarkably, X-chromosome upregulation and X-chromosome inactivation are developmentally regulated, and are reversed in the embryo during development. However, this reversal can also be induced by reprogramming specialized cells such as skin cells into stem cells, which can then make any other cell type. These processes are an ideal model to understand how genes are turned on and off, as well as how the dosage of genes is maintained at normal levels. In this project, I will use a system in which, after inducing specialized cells to become stem cells, I will be able to track the activity of all genes taking part in this transition. Additionally, I will identify factors important for genes to be expressed at the correct dose. By using new technologies, my work will give a wide, comprehensive view on these fundamental mechanisms, and will help in the derivation of high quality stem cells, which in turn, will contribute to the progress in reproductive, regenerative, developmental, and cancer medicine.