Turning on Myogenin in Muscle: A Paradigm for Understanding Mechanisms of Tissue-Specific Gene Expression

Figure 3

Model for the regulation of Myog gene expression. The model summarizes current knowledge of the regulation of Myog gene expression. See main body of the text for details. The first column highlights the different steps of myogenic differentiation. The muscle stem cell/progenitors (dark blue cell) undergo commitment to the muscle lineage (light blue cell), then proliferate (dark green cell), differentiate into myocytes (purple cell), and fuse with each other to form myofibers, the functional unit of the muscle. The second column highlights the role of DNA binding transcription factors at the myogenin promoter. The boxes correspond to the DNA binding site for the specific transcription factors: CCGG repeat (C, grey); E-box (E, blue); Pbx1b (P, orange) Mef3 (M, red); Mef2 (M, pink); TATA box (T, green). DNA methylation is represented by white stars and the transcription factors which bind the DNA elements are coded by colored circle. Transcriptional repression and activation are indicated by OFF and ON, respectively. The light black arrows indicate low-level transcription, while the thick black arrows represent strong transcription. The third column represents the regulation of Myog through histone modifications. The nucleosome is represented by circles: grey (Histone H4), medium grey (the Histone H2A/H2B core), dark grey (Histone H3). Deacetylation of the lysine is represented by pink stars (deAC), while acetylation (Ac) is indicated by orange stars. Modifications of histone H3 map as colored lollipops indicates: monomethylation (Me1), dimethylation (Me2), trimethylation (Me3), and phosphosrylation (P) of specific amino acids. The histone modifying enzymes are represented by colored circles (methyltransferase, acetyltransferases and kinases) or colored crosses (deacetylases and demethylases). The smaller circles represent the transcription factors: MyoD (blue), Mef2 (pink), and Six (brown). The fourth column represents regulation of chromatin structure. Nucleosomes are represented by the black DNA wrapped around grey cylinders (histone octamers): heterochromatin (tightly packed nucleosomes) and euchromatin (spaced nucleosomes). The SWI/SNF subunits are represented as colored circles. The smaller circles represent the transcription factor MyoD (blue).