MyoD

MyoD, which was discovered in the laboratory of Harold M. Weintraub,[6] belongs to a family of proteins known as myogenic regulatory factors (MRFs).

[8][9] MyoD was cloned by a functional assay for muscle formation reported in Cell in 1987 by Davis, Weintraub, and Lassar.

The function of MyoD in development is to commit mesoderm cells to a skeletal myoblast lineage, and then to regulate that continued state.

[12] MyoD is also an important effector for the fast-twitch muscle fiber (types IIA, IIX, and IIB) phenotype.

Evidence for this model is that reduction of Setdb1 results in direct inhibition of myoblast differentiation which may be caused by the release of the unknown MyoD inhibitor.

MyoD has also been shown to function cooperatively with the tumor suppressor gene, Retinoblastoma (pRb) to cause cell cycle arrest in the terminally differentiated myoblasts.

Cell cycle arrest (in which myoblasts would indicate the conclusion of myogenesis) is dependent on the continuous and stable repression of the D1 cyclin.

Specifically, Wnt3a can directly induce MyoD expression via cis-element interactions with a distal enhancer and Wnt response element.

[20] Wnt1 from dorsal neural tube and Wnt6/Wnt7a from surface ectoderm have also been implicated in promoting myogenesis in the somite; the latter signals may act primarily through Myod.

In typical adult muscles in a resting condition (absence of physiological stress) the specific Wnt family proteins that are expressed are Wnt5a, Wnt5b, Wnt7a and Wnt4.

Wnt plays a crucial role in satellite cell regulation and skeletal muscle aging and also regeneration.

Whether MyoD is activated by Wnt via cis-regulation direct targeting or through indirect physiological pathways remains to be elucidated.

[22][23] NFATc1 is a transcription factor that regulates composition of fiber type and the fast-to-slow twitch transition resulting from aerobic exercise requires the expression of NFATc1.

MyoD associatively binds to the enhancer region in conjunction with a placeholding "putative pioneer factor" which helps to establish and maintain a both of them in a specific and inactive conformation.

Stdb1/MyoD possible pathway.
Evidence suggests that Setdb1 inhibits a repressor of MyoD and this is the mechanism through which MyoD expression is retained in differentiated myoblasts.
Recruitment of transcription factors by MyoD.
MyoD works with a transient placeholder protein that functions to prevent other transcription factors from binding to the DNA and also retains an inactive conformation for the DNA. Once the placeholder is removed (or possibly deactivated) the necessary transcription factors are free to bind and initiate recruitment of RNA Polymerase II and initiate active RNA transcription.