Symmetry Breaking at X-Chromosome Inactivation

Mario Nicodemi, Dipartimento di Scienze Fisiche-Universita' di Napoli "Federico II"

In mammal female cells X-Chromosome Inactivation (XCI) is the process whereby one X, randomly chosen, is silenced to compensate dosage of X products with respect to males. XCI is governed by the X Inactivation Center (Xic), a locus including an array of non-coding genes which interact with each other and with a set of key molecular factors, such as pluripotency factors. The opposite fate of the X's is coupled to changes in the Xic architecture whose conformation is modified in different directions on the future active and inactive X by the action of a yet unknown symmetry breaking mechanism. We investigated a model of the Xic by computer simulations. Interpretation of our results and their comparison against available experimental data highlights the physical mechanisms whereby the locus can spontaneously self-organize through the complex pattern of changes leading to the random, yet mutually exclusive X choice of fate. Our analysis indicates the presence of a key cis-regulatory region which orchestrates functional contacts between the Xic elements; it also predicts non-linear threshold effects of, e.g., genetic deletions in the locus.