Expression of the myogenin (Myog) gene is restricted to skeletal muscle cells where the transcriptional activator turns on a gene expression program that permits the transition from proliferating myoblasts to differentiating myotubes. The strict temporal and spatial regulation on Myog expression in the embryo makes it an ideal gene to study the developmental regulation of tissue-specific expression. Over the last 20 years, our knowledge of the regulation of Myog expression has evolved from the identification of the minimal promoter elements necessary for the gene to be transcribed in muscle, to a mechanistic understanding of how the proteins that bind these DNA elements work together to establish transcriptional competence. Here we present our current understanding of the developmental regulation of gene expression gained from studies of the Myog gene. 1. Introduction The diploid human genome encodes the genes required to establish the ~200 different cell types that make up the body. Each of these different cell types can be defined by the complement of genes that they express. These cell-specific gene expression programs are established through spatially and temporally defined signals from hormones, cytokines, and growth factors that modulate transcription factor activity. Once established, these gene expression programs must then be transmitted to daughter cells through epigenetic mechanisms. Studies in Drosophila have identified Trithorax (TrxG) and Polycomb (PcG) group proteins as the mediators of this epigenetic cellular memory [1]. However, the PcG and TrxG proteins display relatively ubiquitous expression and therefore cannot work in isolation to mediate temporal and spatial regulation of gene expression. Thus, in order to understand how tissue specific patterns of gene expression are established we must examine how the TrxG and PcG proteins work with the transcriptional machinery in specific cells to modulate expression of a particular gene. The skeletal muscle-specific gene myogenin (Myog) is a key developmental regulator for skeletal muscle formation and is one of the better studied tissue-specific genes. The Myog gene encodes a transcription factor of the basic-helix-loop-helix (bHLH) protein family. Displaying expression that is highly restricted, both temporally and spatially, Myog transcripts are first detected in the primary myotome of the developing mouse embryo at around day E9 [2, 3]. Myog then continues to be expressed in all the newly formed skeletal muscle of the trunk and the limb bud during embryonic myogenesis before being
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