The myoD Gene Family: Nodal Point During Specification of the Muscle Cell Lineage

Abstract

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.

Functional specificity of the two retinoic acid receptor RAR and RXR families in myogenesis

“…MyoD has been implicated as a master regulatory gene in the process of muscle di erentiation: it is su cient to induce withdrawal from cell cycle and expression of muscle di erentiation markers (Crescenzi et al, 1989;Sorrentino et al, 1990;Weintraub et al, 1991). These two myogenesis-related events are also regulated by retinoic acid suggesting that RA-receptors and MyoD might act in the same regulatory pathway governing the RA-induced myogenesis.…”

Mechanisms of Lung Fibrosis Resolution

“…40,41,48e59 MyoD is a master transcriptional regulator of myogenic differentiation and mediates TGF-b1einduced myofibroblast differentiation of human lung fibroblasts. 40,60 Down-regulation of endogenous MyoD with RNA interference in myofibroblasts was associated with dedifferentiation and increased proliferation. 40 TGF-b1estimulated normal human lung fibroblasts incubated with fibroblast growth factor-1 demonstrate reduced collagen gel contraction and a significant decrease c-FLIP, c-Fas-like IL 1b-converting enzymeeinhibitory protein; FGF, fibroblast growth factor; IPF, idiopathic pulmonary fibrosis; MRTF, myocardin-related transcription factor; MyoD, myoblast determination protein 1; NFA, nitrated fatty acid; Nrf2, nuclear factor erythroid 2-related factor 2; PAI, plasminogen activator inhibitor; PGE, prostaglandin E; PI3K, phosphatidylinositol 3-kinase; PPAR, peroxisome proliferator-activated receptor; ROCK, Rho-associated kinases; SRF, serum response factor; TGF, transforming growth factor; XIAP, X-linked inhibitor of apoptosis.…”

p53 protein is activated during muscle differentiation and participates with MyoD in the transcription of muscle creatine kinase gene

“…Ectopic expression of MyoD in NIH3T3 ®broblast cells converts them to muscle cells that express muscle-speci®c genes (Weintraub et al, 1991a). To study the e ect of dominant negative p53 protein in another cellular system, we transfected NIH3T3 ®broblasts with MyoD and p53 proteins.…”

“…Two groups of muscle-speci®c transcription factors were shown to be involved in the transcription of MCK. The ®rst is the MyoD family that is involved in the activation of many musclespeci®c genes and therefore plays a pivotal role in driving the myogenic developmental process (reviewed in Weintraub et al, 1991a). The second is the MEF2 family that is not speci®c to muscle but plays an important role in the transcription of many musclespeci®c genes, including myogenin that belongs to the MyoD family.…”