The myoD gene converts many differentiated cell types into muscle. MyoD is a member of the basic-helix-loop-helix family of proteins; this 68-amino acid domain in MyoD is necessary and sufficient for myogenesis. MyoD binds cooperatively to muscle-specific enhancers and activates transcription. The helix-loop-helix motif is responsible for dimerization, and, depending on its dimerization partner, MyoD activity can be controlled. MyoD senses and integrates many facets of cell state. MyoD is expressed only in skeletal muscle and its precursors; in nonmuscle cells myoD is repressed by specific genes. MyoD activates its own transcription; this may stabilize commitment to myogenesis.

https://science.sciencemag.org/content/sci/251/4995/761.full.pdf

The myoD gene family: nodal point during specification of the muscle cell lineage

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins

Accumulating evidence implicates the transcription factor NF-kappaB as a positive mediator of cell growth, but the molecular mechanism(s) involved in this process remains largely unknown. Here we use both a skeletal muscle differentiation model and normal diploid fibroblasts to gain insight into how NF-kappaB regulates cell growth and differentiation. Results obtained with the C2C12 myoblast cell line demonstrate that NF-kappaB functions as an inhibitor of myogenic differentiation. Myoblasts generated to lack NF-kappaB activity displayed defects in cellular proliferation and cell cycle exit upon differentiation. An analysis of cell cycle markers revealed that NF-kappaB activates cyclin D1 expression, and the results showed that this regulatory pathway is one mechanism by which NF-kappaB inhibits myogenesis. NF-kappaB regulation of cyclin D1 occurs at the transcriptional level and is mediated by direct binding of NF-kappaB to multiple sites in the cyclin D1 promoter. Using diploid fibroblasts, we demonstrate that NF-kappaB is required to induce cyclin D1 expression and pRb hyperphosphorylation and promote G(1)-to-S progression. Consistent with results obtained with the C2C12 differentiation model, we show that NF-kappaB also promotes cell growth in embryonic fibroblasts, correlating with its regulation of cyclin D1. These data therefore identify cyclin D1 as an important transcriptional target of NF-kappaB and reveal a mechanism to explain how NF-kappaB is involved in the early phases of the cell cycle to regulate cell growth and differentiation.

NF-κB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1

Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor

https://www.cell.com/cell/pdf/0092-8674(91)90620-E.pdf

Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo

https://www.cell.com/cell/pdf/0092-8674(89)90101-3.pdf

Robert W. Overell

Papers

Transformation by activated ras or fos prevents myogenesis by inhibiting expression of MyoD1.