DoseX

Inactivation of one of the two X chromosomes present in females is essential to ensure dosage compensation between XX females and XY males. This epigenetic process is controlled by a large locus (Xic) comprising several protein coding genes and long non-coding RNAs. Despite recent important progresses, it is still unclear how cells determine the number of X chromosomes present and stably inactivate all but one. With a series of mice carrying engineered rearrangements altering the number of elements composing the Xic, their relative position or even the overall structure of this chromosome, we will determine their role as well as the contribution of the 3D-conformation of the inactive X in the different steps of this process. We will also study a series of mouse lines carrying large duplications of the X chromosome to study in vivo the physiological consequences of dosage imbalance and identify dosage-sensitive genes that contribute to X-linked genetic pathologies in humans