| Summary: | 碩士 === 國立中央大學 === 生命科學研究所 === 93 === Determination of myogenic lineage is dictated by the function of bHLH transcription factors of MRF (Myogenic Regulatory Factor) family, which consists of MyoD, Myogenin, Myf-5 and MRF-4, and they are also the major factors regulating terminal differentiation of muscle cells. Overexpression of any one of the MRF family in several non-myogenic cells can induce their trans-differentiation into myogenic lineage. However, myoblsts differentiate into mature muscle cells still need the help of MEF-2 (Myocyte Enhancer Factor-2). MEF-2 proteins can cooperate with myogenic bHLH proteins as a heterodimer to regulate the expression of muscle-specific genes and commit myoblasts to terminal differentiation. Another factor, FKHR, also plays a role in terminal differentiation by promoting the fusion of myoblasts which is the essential process of myoblasts differentiation. Recently, PGC-1α (Peroxisome proliferator-activated receptor PPAR-γ Coactivator-1α) was shown to promote the formation of slow-twitch fibers, and which is regulated by MEF2 and FKHR. Since MEF-2 and FKHR are both implicated in the terminal muscle differentiation, it prompts us to study the regulation of PGC-1α in muscle by other muscle-specific transcription factors, such as MyoD and its family members. Here we show that MyoD can activate PGC-1α expression by binding to two putative E-boxes localized to its core promoter. Mutation of either site significantly reduced MyoD mediated transactivation. We also found out that when myoblast differentiates into myotube the expression of PGC-1α is up-regulated. The expression of PGC-1α also increased in retrovirus-mediated MyoD-overexpressed cells when they differentiate into myotubes. Since PGC-1α is suggested to be the principle factor regulating muscle fiber type determination, our results indicate that MyoD is not only involved in the lineage determination and terminal differentiation, but may also implicated in the fiber-type and metabolic switch of mature muscle cells.
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