The formation of mature tissues and cell types in eukaryotic organisms requires that cells undergo a regulated series of steps leading to terminal cell differentiation, which includes a permanent withdrawal from the cell cycle and the eventual cessation of all cell proliferation. Concomitant with this process is the stable repression of many genes involved in normal cell growth and cell cycle control, accompanied by profound changes in nuclear chromatin structure that arise as previously active genes gradually become silenced and are modified epigenetically to form facultative heterochromatin (Grigoryev et al. 2006). At the same time, newly activated signaling pathways must induce the de novo expression, function, or nuclear localization of the various tissue-specific enhancer-binding proteins needed to regulate the genes responsible for creating and maintaining the differentiated cell phenotype. A powerful system used to identify the fundamental principles of cell fate specification is the process of skeletal muscle differentation, or myogenesis, in which multipotential mesodermal precursor cells commit and differentiate to a muscle cell fate (Sartorelli and Caretti 2005). This process can be studied in defined sequential stages, wherein the precursor cells first commit to form undifferentiated myoblasts, then differentiate and fuse to form multinucleated myotubes, and subsequently mature into functional myofibers. Key upstream activators in this process include members of t