Abstract
X-chromosome inactivation has long served as an experimental model system for understanding the epigenetic regulation of gene expression. Central to this phenomenon is the long, non-coding RNA Xist that is specifically expressed from the inactive X chromosome and spreads along the entire length of the chromosome in cis. Recently, two of the proteins originally identified as components of the nuclear scaffold/matrix (S/MAR-associated proteins) have been shown to control the principal features of X-chromosome inactivation; specifically, context-dependent competency and the chromosome-wide association of Xist RNA. These findings implicate the involvement of nuclear S/MAR-associated proteins in the organization of epigenetic machinery. Here, we describe a model for the functional role of S/MAR-associated proteins in the regulation of key epigenetic processes.