The master regulator of muscle differentiation¹, MyoD, functions early in myogenesis肌发生，肌细胞生成 to help stem cells proliferate增殖，扩散 in response to muscle injury, according to researchers at Case Western Reserve University. The study appears online Jan. 4 in the Journal of Cell Biology (www.jcb.org). MyoD is a transcription factor转录因子 that activates⁶ muscle-specific genes³ as myoblast成肌细胞 precursors前体细胞 differentiate⁸ and fuse融化，融合 to form mature muscle fibers⁹. But MyoD is also expressed at an earlier stage of myogenesis when quiescent¹⁰静止的，沉寂的 stem cells rapidly expand in number to generate the myoblasts needed to repair tissue damage. The transcription factor's function in this proliferative¹¹ phase is unknown.

The team found that MyoD bound to the promoter of CDC6, a gene² that initiates¹² DNA¹³ replication, suggesting that MyoD might activate⁵ Cdc6 expression in muscle stem cells to promote their reentry into the cell cycle and rapid proliferation. Indeed, Cdc6 was expressed shortly after MyoD in stimulated¹⁴ muscle progenitors¹⁵, and knocking down MyoD reduced Cdc6 production and slowed cells' entry into S phase. MyoD works in conjunction with transcription factors from the E2F family. E2F3a activated¹⁶ the CDC6 promoter with MyoD, but was replaced by the repressive family member E2F4 as myoblasts began to differentiate.

Senior author Nikki Harter now wants to investigate how the transcription factors cooperate to control Cdc6 expres-sion—initial results suggest that MyoD recruits E2F3a to the promoter region. The researchers also propose that a related protein, Myf5, might control Cdc6 transcription in MyoD's absence, acting¹⁷ as a backup mechanism¹⁸ to ensure that muscle stem cells expand to repair tissue damage.