Skeletal myogenesis depends on the strict regulation of the expression of various gene subsets. Therefore, the understanding of genome wide gene regulation is imperative for elucidation of skeletal myogenesis. In recent years, systems approach has contributed to the understanding of various biological processes. Our group recently revealed the critical genome network of skeletal myogenesis by using a novel systems approach combined with whole-mount in situ hybridization (WISH) database, high-throughput screening, and microarray analysis. In this paper, we introduce our systems approach for understanding the myogenesis regulatory network and describe the advantages of systems approach. 1. Introduction Skeletal muscle is indispensable for any moving function of the human body, and abnormality of the skeletal muscle causes great disability in affected people. It is therefore important to understand the mechanism of skeletal myogenesis so that it may form a basis for disease treatment. Almost all skeletal muscles in the body derive from dermomyotome or myotome in somites. The myotome and dermomyotome contain myogenic progenitor cells that evolve into skeletal muscles, aggregates of myofibers, in the whole body. During skeletal myogenesis, myofibers form from myogenic progenitors, where distinct subsets of genes are activated or repressed and form a complex molecular network of interdependent pathways [1–3]. These processes are mainly regulated by the muscle-specific basic helix-loop-helix (bHLH) transcription factors, MyoD, Myf5, Myogenin (Myog), and Mrf4. Analysis of null mice of these genes suggested that MyoD and Myf5 play a role in determining the myogenic progenitors to myoblasts [4]. Myog is important in differentiation from myoblasts to myotubes [5, 6], and Mrf4 is important in both determination and differentiation [7]. The described transcription factors are class II (tissue-specific) bHLH transcription factors capable of either homodimerization or heterodimerization with class I bHLH factors, such as E-proteins HEB/HTF4, E2-2/ITF-2, and E12/E47 [8]. All bHLH dimers bind to an E-box, a consensus sequence comprised of the sequence CANNTG. Id proteins have been identified to act as myogenic antagonists by directly binding to E-proteins and/or muscle-specific bHLH proteins, blocking their ability to bind E-boxes and activate transcription at muscle-specific promoters [9–11]. IdmRNAs are detected in proliferating skeletal muscles and are downregulated in differentiated muscle cultures [9, 12]. This downregulation was thought to be important for
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