Abstract IA10: Spreading of X-chromosome inactivation via a hierarchy of defined Polycomb stations

Abstract X-chromosome inactivation (XCI) achieves dosage balance in mammals by repressing one of two X-chromosomes in females. During XCI, the long noncoding Xist RNA and Polycomb proteins spread along the inactive X (Xi) to initiate chromosome-wide silencing. Although inactivation is known to commence at the X-inactivation center (Xic), how it propagates remains unknown. We have examined allele-specific binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during XCI, and generate a chromosome-wide profile of Xi and Xa (active X) at nucleosome-resolution. Initially, Polycomb proteins are localized to a limited number of sites along the X. As Xist RNA spreads in cis during the XCI process, thousands of additional sites are recruited. PRC2 and H3K27 methylation spread along a gradient in an Xi-specific manner not seen on autosomes. Our findings suggest that XCI is governed by a hierarchy of defined Polycomb stations that spread H3K27 methylation in cis . Citation Format: Stefan F. Pinter, Yesu Jeon, Toshiro K. Ohsumi, Mark Borowsky, Jeannie T. Lee, Ruslan I. Sadreyev, Eda Yildirim. Spreading of X-chromosome inactivation via a hierarchy of defined Polycomb stations [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA10.