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姓名	高健涵(Chien-han Kao)  查詢紙本館藏	畢業系所	生命科學系
論文名稱	E-boxes參與MyoD活化M-cadherin的轉錄 與 Stra13調控PGC-1α的轉錄活化能力 (The involvement of E-boxes in MyoD-mediated M-cadherin activation and the modulation of PGC-1α transactivational ability by Stra13)
相關論文	★ Thirst control of water-seeking behavior in Drosophila ★ KLHL17在癲癇與自閉症中之角色 ★ MyoD對於PGC-1α 基因表現之調控機制 ★ 雄性素受體對於肌肉前驅細胞決定的功用 ★ Nanog和Oct4表現對肌肉分化之影響 ★ 大量表現幹細胞專有轉錄因子抑制肌肉細胞走向分化 ★ FOXOs 轉錄調控因子家族對肌肉細胞末期分化的影響 ★ 大量表現 Oct4 與 Nanog 抑制肌纖維母細胞 C2C12 分化 ★ 在終極肌肉分化時，肌肉性bHLH轉錄因子對PGC-1α的調控 ★ FoxOs 大量表現對肌肉細胞末期分化的影響 ★ 觀察肌肉生成轉錄因子如何調控 Ｍ- 和Ｎ- cadherin 表現 ★ Oc4和Nanog共同抑制末端肌肉分化 ★ FoxO6在肌原母細胞中的代謝及分化中所扮演的角色 ★ PGC-1α 與 Stra13 間之交互作用 ★ 探討大量表現 FoxO6 對肌肉終極分化的影響以及尋找 FoxO6 蛋白質在 PGC-1 alpha 啟動子上的結合位 ★ 探討丙戊酸 (Valporic acid) 於肌肉細胞中活化 Oct4 promoter 的機制
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摘要(中)	E-boxes參與MyoD活化M-cadherin的轉錄 肌肉調節因子(MRF)家族已被證實，可以透過辨認促進子(E-box)來調控肌肉細胞命運的決定及肌管的形成。 在肌肉發育的過程中，肌肉調節因子透過辨認啟動子上的促進子來活化肌肉相關基因的轉錄。 過去的研究顯示，MyoD可以透過辨認M-cadherin近端啟動子(-252~+200 bp)上的促進子來活化M-cadherin的轉錄。 在M-cadherin近端啟動子上，已知有五個促進子，單一促進子突變的結果顯示，第四號促進子(E-box 4)為M-cadherin啟動子上最為重要的促進子。 因此，對於促進子間的交互作用是否影響MyoD調控M-cadherin的轉錄，仍有待進一步的調查。 最近的實驗結果顯示，除了第四號促進子，第三號促進子(E-box 3)對於MyoD活化M-cadherin的轉錄也十分的重要。 此外，MyoD活化M-cadherin轉錄的效率，可能與啟動子上促進子的數量有關，一旦同時突變超過三個以上的促進子，MyoD活化M-cadherin轉錄的能力將大幅的下降。 實際上，在正常的生理狀態下，MyoD通常會與E47結合，並以二聚體的形式來作用。 因此，為了模擬生理狀態下MyoD的功能，透過一小段具有伸縮性的胺基酸鏈來連結MyoD與E47，以強迫MyoD與E47形成二聚體，此人為修飾的肌肉調節因子MyoD~E47，除了較自然的肌肉調節因子具有更強力的轉錄活化能力之外，還能有效避免細胞內抑制子與MyoD結合。 儘管MyoD~E47相較於MyoD來說，確實可以顯著提升M-cadherin的轉錄效率。 但是MyoD~E47仍無法克服在M-cadherin啟動子上需要三個以上的促進子來完全活化M-cadherin的轉錄。 總結來說，在M-cadherin啟動子上，促進子與MyoD之間確實存著交互作用，但是詳細的調控機制仍有待進一步釐清。 Stra13調控PGC-1α的轉錄活化能力 粒腺體透過進行有氧呼吸來產生高能的三磷酸腺苷(ATP)，用以提供無數細胞活動與生存所需的能量。 PGC-1α已被報導可以協同細胞核上的受體(nuclear receptors)來共同調控粒線體的增生與功能。 除了調節粒線體的功能與數量外，PGC-1α也被證實參與了抗氧化及代謝方面的調控。 最近我們實驗室有了一個嶄新的發現，PGC-1α可以與basic helix-loop-helix (bHLH)家族的抑制子Bhlhe40或稱為Stra13產生交互作用。 由於PGC-1α的重要性， Stra13是否會影響PGC-1α所調控的細胞功能是一個值得探討的問題。 實驗結果指出，在Stra13 knockdowned的肌纖維母細胞(C2C12)中， PGC-1α下游基因的轉錄發生了改變。 除此之外，提升的PGC-1α轉錄活化能力，同樣也在Stra13 knockdowned的肌纖維母細胞中被證實。 在生理功能的調控上，Stra13 knockdowned的肌纖維母細胞相較於正常細胞，擁有更多的細胞內自由基(ROS)與減少的粒線體模電位。 增加的氧氣消耗與粒線體數量顯示出，在Stra13 knockdowned的肌纖維母細胞中，粒腺體可能處在一個比較為活躍的狀態。 另一方面，減少的基礎及胰島素誘導的葡萄糖運輸與增加的棕梠酸代謝暗示著，在Stra13 knockdowned的肌纖維母細胞中，細胞對營養利用的偏好可能發生了改變。 就結果來說，Stra13的影響範圍十分廣泛，幾乎影響了全部PGC-1α所參與的調控。 但是，關於這些結果是源於減輕Stra13對PGC-1α的抑制所造成，抑或僅僅只是失去內生性的Stra13所造成的影響，至今尚未十分明瞭，仍有待進一步的釐清。
摘要(英)	The involvement of E-boxes in MyoD-mediated M-cadherin activation The muscle regulatory factor (MRF) family has been known to regulate myogenic cell lineage determination and terminal differentiation of myotubes through targeting consensus enhancer box (E-box). Targeting of MRFs to E-boxes presented in promoter or enhancer region of myogenic genes is important for controlling myogenesis process. According to previous study, MyoD was able to target E-boxes around M-cadherin proximal promoter (-252~+200bp) to activate M-cadherin transcription. There are five defined E-boxes in M-cadherin proximal promoter, and reporter result of single E-box mutation showed that E-box 4 is the most important E-box in M-cadherin promoter. Furthermore, it is of interest to investigate whether the cross-talk between E-boxes and MyoD influences MyoD-mediated M-cadherin activation. Recently, our results showed that besides E-box 4, E-box 3 is also an important E-box for MyoD-mediated M-cadherin activation. Moreover, the efficiency of MyoD transactivating M-cadherin may be related to the E-box number presented in promoter region. Once more than three E-boxes were mutated, the ability of MyoD to transactivate M-cadherin transcription would significantly reduce. Indeed, MyoD prefers to form heterodimer with E47 to function in physical condition. Therefore, the dominant positive myogenic factor, MyoD~E47 tethered protein, was used to mimic physical condition of MyoD function. Although MyoD~E47 tethered protein could significantly enhance M-cadherin transcription when compared to MyoD, but it was unable to overcome that more than three E-boxes were required to fully activate M-cadherin transcription. Taken together, the cross-talk between E-boxes and MyoD is certainly present, but detailed mechanism is still waiting to be clarified. The modulation of PGC-1α transactivational ability by Stra13 Mitochondria-mediated oxidative respiratory is essential for generating high energy ATP for numerous cellular processes. Peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) had been reported to synergize with several nuclear receptors to control mitochondrial biogenesis and function. Besides mitochondria modulation, PGC-1α had been proved to be involved in anti-oxidation and metabolism modulation. Recently, our lab identified a novel interaction between PGC-1α and basic helix-loop-helix (bHLH) repressor, Bhlhe40 or called Stra13. Due to the importance of PGC-1α, it is of interest to investigate the effect of Stra13 on PGC-1α-regulated cellular processes. Results had indicated that altered expression of PGC-1α targets were observed in Stra13 knockdowned C2C12 cells. Moreover, PGC-1α have showed a better transactivation ability in Stra13 knockdowned C2C12 cells. In physiological modulation respect, Stra13 knockdowned C2C12 cells showed a burst of ROS but a reduced mitochondrial membrane potential. Moreover, increased mitochondria content and oxygen consumption implied that mitochondria in Stra13 knockdowned C2C12 cells is likely to be at a more active state. On the other hand, a regressive basal and insulin-induced glucose uptake but an improved palmitic acid oxidation in Stra13 knockdowned C2C12 cells suggests that a switch of nutrient utilization occurred. Consequently, the effect of Stra13 is extensive, and almost all of PGC-1α-involved regulation have been affected and changed. However, it is still unclear that those observations were resulted from relieving Stra13-mediated PGC-1α functional inhibition or just an unspecific effect of loss endogenous Stra13.
關鍵字(中)	★ 轉錄調控	關鍵字(英)	★ MyoD ★ E-box ★ M-cadherin ★ PGC-1a ★ Stra13
論文目次	中文摘要 7~8 Abstract 9~10 Declaration 11 Acknowledgement 12~13 Table of Contents 13~20 I. Introduction 21~37 Part 1 (The involvement of E-boxes in MyoD-mediated M-cadherin activation) 21~27 I-1-1 Outline I-1-2 Functional domains of bHLH proteins I-1-3 Introduction of MRF members I-1-4 Relationship between E-boxes and MRFs in muscle regulation I-1-5 Involvement of E-proteins in myogenesis I-1-6 Id, the negative regulator of MRFs I-1-7 MyoD~E47 tethered protein, a dominant positive myogenic factor I-1-8 General introduction of cadherin I-1-9 Importance of M-cadherin in muscle differentiation I-1-10 Involvement of M-cadherin in muscle regeneration Part 2 (The modulation of PGC-1α transactivational ability by Stra13) 28~37 I-2-1 Outline I-2-2 Discovery of PGC-1α and involvement of it in adaptive thermogenesis I-2-3 Functions of PGC-1 members in mitochondrial biogenesis I-2-4 PGC-1 members synergized with nuclear receptors (NRF1, NRF2, ERRα) to prompt mitochondrial biogenesis I-2-5 PGC-1 members synergized with nuclear receptors (PPARs, ERRα) to regulate nutrient metabolism I-2-6 Relationship between PGC-1α activity and post-translational modification I-2-7 Mechanism for Stra13 function I-2-8 Relationship between PGC-1α and Stra13 II. Materials and Methods 38~64 II-1 Cloning strategies II-1-1 Restriction enzyme digestion II-1-2 Polymerase (Taq and Pfu) II-1-3 klenow II-1-4 PNK (T4 Polynucleotide Kinase) II-1-5 Cip (Alkaline Phosphatase, Calf Intestinal) II-1-6 Ligase II-1-7 Site directed mutagenesis by overlapping PCR II-2 Clone list II-3 Transfection II-4 Luciferase assay Total protein extraction II-5 total protein extraction II-6 Western blot II-7 RNA extraction II-8 Reverse transcription-polymerase chain reaction (RT-PCR) II-9 Quantitative real-time PCR (qRT-PCR) II-10 shRNA lentiviral production II-11 shRNA lentiviral infection II-12 Mechanism for generating a safe lentiviral particle by plasmids II-13 Reactive oxygen species (ROS) measurement II-14 Mitochondrial membrane potential (Δψm) measurement II-15 Intracellular NAD(P)H content measurement II-16 Genomic DNA extraction II-17 Mitochondria content determination II-18 Glucose uptake II-19 Fatty acid oxidation II-20 Intracellular ATP content measurement II-21 Winkler test for dissolved oxygen measurement II-22 ChIP assay II-22-1 Step1 (cell harvest) II-22-2 Step2 (chromatin immunoprecipitation) II-22-3 Step3 (isolation and purification of genomic DNA fragments) II-23 Sequential ChIP assay III. Result 65~98 Part 1 (The involvement of E-boxes in MyoD-mediated M-cadherin activation) 65~70 III-1-1 M-cadherin core promoter with various E-boxes mutation were constructed III-1-2 E-boxes in M-cadherin core promoter have different importance III-1-3 E-box 3 is another essential E-box for MyoD-mediated M-cadherin activation III-1-4 At least three E-boxes are required to fully activate M-cadherin transcription by MyoD III-1-5 Mimic the physiological condition of MyoD function by MyoD~E47 tethered protein III-1-6 The activity of M-cadherin promoter is determined by E-box number instead of the intensity of activator III-1-7 Different myogenic promoter have different competence to regulate the dimerization process between MyoD and E-proteins III-1-8 M-cadherin core promoter with various E-boxes mutation were constructed Part 2 (The modulation of PGC-1α transactivational ability by Stra13) 71~98 III-2-1 Monoclone of C2C12-shStra13 was established to investigate the physiological meaning of Stra13 and PGC-1α interaction in skeletal muscle III-2-2 Expression of potential targets of PGC-1α were investigated by RT-PCR or qRT-PCR in C2C12-shStra13 and control cells III-2-2-1 Reduced expression of endogenous Stra13 can enhance PGC-1α transcription III-2-2-2 Stra13 may be involved in the transcriptional control of ETC complex III-2-2-3 Knockdown of Stra13 does not affect TFAM transcription III-2-2-4 A switch of nutrient metabolism is observed in C2C12-shStra13 cells III-2-2-5 A markedly reduced Cat and Sod2 expression are observed in C2C12-shStra13 cells III-2-2-6 Terminal differentiation markers show a regressive trend in C2C12-shStra13 cells III-2-2-7 Conclusion of preliminary screening results III-2-3 Intracellular ROS level was investigated in C2C12-shStra13 cells III-2-3-1 Reduced expression of endogenous Stra13 leads to a burst of intracellular ROS III-2-3-2 Mitochondria, the major origin of intracellular ROS, was further investigated III-2-3-3 Reduced mitochondrial membrane potential but increased mitochondria content in C2C12-shStra13 cells III-2-3-4 Hypotheses for reduced mitochondrial membrane potential in C2C12-shStra13 cells III-2-3-5 Reduced mitochondrial membrane potential in C2C12-shStra13 cells is unlikely to be caused by reduction of ETC complexes III-2-3-6 Intracellular high-energy substrate, NAD(P)H, is sufficient in C2C12-shStra13 cells III-2-3-7 Reduced mitochondrial membrane potential in C2C12-shStra13 cells may be resulted from activation of uncoupling proteins III-2-4 Metabolic features were investigated in C2C12-shStra13 cells III-2-4-1 A reduced basal and insulin-induced glucose uptakes but an improved PA oxidation in C2C12-shStra13 cells III-2-4-2 More ROS was produced in response to exogenous PA treatment in C2C12-shStra13 cells III-2-4-3 C2C12-shStra13 cells prefer and are more efficient to utilize fatty acid (PA) as energy resource instead of glucose III-2-4-4 Increased oxygen consumption in Stra13 knockdowned C2C12 cells III-2-4-5 Exogenous PA treatment reduces the oxygen consumption in C2C12-shStra13 cells III-2-4-6 Stra13 is an essential factor for modulating peroxisome content in C2C12 cells III-2-5 Stra13-mediated PGC-1α functional inhibition is partly realized by recruiting histone deacetylase (HDACs) to promoter region III-2-6 Improved PGC-1α expression at both mRNA and protein level in mice performed oxidative training III-2-7 Truncated Stra13 fragment (1~135) blocks Stra13-mediated inhibition on potential PGC-1α targets III-2-8 Reduced mitochondria content and intracellular ATP content in VP16-Stra13 1~135 overexpressed C2C12 cells III-2-9 Stra13 can interact with PGC-1α in vivo III-2-10 Establishment of Tet-off system based Stra13 overexpressed C2C12 cells III-2-11 Effects of Stra13 overexpression on PGC-1α-mediated gene regulation and cellular processes IV. Discussion 99~110 Part 1 (The involvement of E-boxes in MyoD-mediated M-cadherin activation) 99~102 Part 2 (The modulation of PGC-1α transactivational ability by Stra13). 103~110 V. Reference 111~118 VI. Figures 119~149 Figure. 1. Cross-talk between E-boxes and MyoD in M-cadherin core promoter Figure. 2. The dominant positive myogenic factor, MyoD~E47 tethered protein, is not enough to fully activate M-cadherin core promoter retaining only E-box 3 and 4, two of the most important E-boxes Figure. 3. Establishment of Stra13 knockdowned C2C12 cells through shRNA Figure. 4. Effects of Stra13 knockdown on mRNA expression of potential PGC-1α targets Figure. 5. Intracellular ROS level and mitochondrial membrane potential were determined in C2C12-shStra13 and control cells Figure. 6. Higher mtDNA/ncDNA ratio and intracellular NAD(P)H in Stra13 knockdowned C2C12 cells Figure. 7. Altered preference of nutrient utilization occurred in Stra13 knockdowned C2C12 cells Figure. 8. General ATP production and oxygen consumption were determined in C2C12-shStra13 and control cells in the present or absent of fatty acid supply Figure. 9. Stra13 is essential for modulating peroxisome content in C2C12 cells Figure. 10. Involvement of HDACs in Stra13-mediated PGC-1α inhibition Figure. 11. Mice performed oxidative training show an enhanced expression of PGC-1α and its targets Figure. 12. Overexpressing truncated Stra13 fragment with VP16 modification is efficient to improve PGC-1α function and its targeted genes expression Figure. 13. Stra13 can interact with PGC-1α in vivo Figure. 14. Effects of Stra13 overexpression on transcription of potential PGC-1α targets and other PGC-1α-regulated cellular processes VII. Appendixes 150~160 VII-1 Solutions VII-2 Primer list VII-3 Other Clone list VII-4 Equilibrium equation and experimental steps of Winkler test VII-5 Scheme of mutagenesis by overlapping PCR VII-6 Outstanding poster award in the Twenty-third Symposium on Recent Advances in Cellular and Molecular Biology
參考文獻	Baffy, G. (2010). Uncoupling protein-2 and cancer. Mitochondrion 10, 243-252. Barbosa, M.R., Sampaio, I.H., Teodoro, B.G., Sousa, T.A., Zoppi, C.C., Queiroz, A.L., Passos, M.A., Alberici, L.C., Teixeira, F.R., Manfiolli, A.O., et al. (2013). Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: effect of catalase overexpression. Biochim Biophys Acta 1832, 1591-1604. Bek, M.J., Wahle, S., Muller, B., Benzing, T., Huber, T.B., Kretzler, M., Cohen, C., Busse-Grawitz, A., and Pavenstadt, H. (2003). Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes. FASEB J 17, 682-684. Belke, D.D., Larsen, T.S., Lopaschuk, G.D., and Severson, D.L. (1999). Glucose and fatty acid metabolism in the isolated working mouse heart. Am J Physiol 277, R1210-1217. Benezra, R., Davis, R.L., Lockshon, D., Turner, D.L., and Weintraub, H. (1990). The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61, 49-59. Blackwell, T.K., and Weintraub, H. (1990). Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science 250, 1104-1110. Brand, M.D., Affourtit, C., Esteves, T.C., Green, K., Lambert, A.J., Miwa, S., Pakay, J.L., and Parker, N. (2004). Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37, 755-767. Cao, Y., Kumar, R.M., Penn, B.H., Berkes, C.A., Kooperberg, C., Boyer, L.A., Young, R.A., and Tapscott, S.J. (2006). Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters. EMBO J 25, 502-511. Chang, C.C., South, S., Warren, D., Jones, J., Moser, A.B., Moser, H.W., and Gould, S.J. (1999). Metabolic control of peroxisome abundance. J Cell Sci 112 ( Pt 10), 1579-1590. Comai, G., and Tajbakhsh, S. (2014). Molecular and cellular regulation of skeletal myogenesis. Curr Top Dev Biol 110, 1-73. Cornelison, D.D., and Wold, B.J. (1997). Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells. Dev Biol 191, 270-283. Davis, R.L., and Weintraub, H. (1992). Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. Science 256, 1027-1030. de Andrade, P.B., Casimir, M., and Maechler, P. (2004). Mitochondrial activation and the pyruvate paradox in a human cell line. FEBS Lett 578, 224-228. Dressel, U., Allen, T.L., Pippal, J.B., Rohde, P.R., Lau, P., and Muscat, G.E. (2003). The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol 17, 2477-2493. Fisher, A.L., Ohsako, S., and Caudy, M. (1996). The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol 16, 2670-2677. Flynn, J.M., and Melov, S. (2013). SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic Biol Med 62, 4-12. Gerhart-Hines, Z., Rodgers, J.T., Bare, O., Lerin, C., Kim, S.H., Mostoslavsky, R., Alt, F.W., Wu, Z., and Puigserver, P. (2007). Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26, 1913-1923. Gulick, T., Cresci, S., Caira, T., Moore, D.D., and Kelly, D.P. (1994). The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci U S A 91, 11012-11016. Hatanaka, E., Dermargos, A., Hirata, A.E., Vinolo, M.A., Carpinelli, A.R., Newsholme, P., Armelin, H.A., and Curi, R. (2013). Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation. PLoS One 8, e58626. Heidt, A.B., Rojas, A., Harris, I.S., and Black, B.L. (2007). Determinants of myogenic specificity within MyoD are required for noncanonical E box binding. Mol Cell Biol 27, 5910-5920. Hsiao, S.P., and Chen, S.L. (2010). Myogenic regulatory factors regulate M-cadherin expression by targeting its proximal promoter elements. Biochem J 428, 223-233. Hsiao, S.P., Huang, K.M., Chang, H.Y., and Chen, S.L. (2009). P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation. Biochem J 422, 343-352. Hulver, M.W., Berggren, J.R., Cortright, R.N., Dudek, R.W., Thompson, R.P., Pories, W.J., MacDonald, K.G., Cline, G.W., Shulman, G.I., Dohm, G.L., et al. (2003). Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 284, E741-747. Irintchev, A., Zeschnigk, M., Starzinski-Powitz, A., and Wernig, A. (1994). Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Dev Dyn 199, 326-337. Ivashchenko, O., Van Veldhoven, P.P., Brees, C., Ho, Y.S., Terlecky, S.R., and Fransen, M. (2011). Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk. Mol Biol Cell 22, 1440-1451. Kliewer, S.A., Sundseth, S.S., Jones, S.A., Brown, P.J., Wisely, G.B., Koble, C.S., Devchand, P., Wahli, W., Willson, T.M., Lenhard, J.M., et al. (1997). Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 94, 4318-4323. Koves, T.R., Ussher, J.R., Noland, R.C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J.R., Newgard, C.B., et al. (2008). Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7, 45-56. Kumar, D., Shadrach, J.L., Wagers, A.J., and Lassar, A.B. (2009). Id3 is a direct transcriptional target of Pax7 in quiescent satellite cells. Mol Biol Cell 20, 3170-3177. Lai, L., Leone, T.C., Zechner, C., Schaeffer, P.J., Kelly, S.M., Flanagan, D.P., Medeiros, D.M., Kovacs, A., and Kelly, D.P. (2008). Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev 22, 1948-1961. Lehman, J.J., Barger, P.M., Kovacs, A., Saffitz, J.E., Medeiros, D.M., and Kelly, D.P. (2000). Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106, 847-856. Lelliott, C.J., Medina-Gomez, G., Petrovic, N., Kis, A., Feldmann, H.M., Bjursell, M., Parker, N., Curtis, K., Campbell, M., Hu, P., et al. (2006). Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance. PLoS Biol 4, e369. Leone, T.C., Lehman, J.J., Finck, B.N., Schaeffer, P.J., Wende, A.R., Boudina, S., Courtois, M., Wozniak, D.F., Sambandam, N., Bernal-Mizrachi, C., et al. (2005). PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3, e101. Londhe, P., and Davie, J.K. (2011). Sequential association of myogenic regulatory factors and E proteins at muscle-specific genes. Skelet Muscle 1, 14. Ma, P.C., Rould, M.A., Weintraub, H., and Pabo, C.O. (1994). Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Cell 77, 451-459. Massari, M.E., and Murre, C. (2000). Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20, 429-440. Mirebeau-Prunier, D., Le Pennec, S., Jacques, C., Gueguen, N., Poirier, J., Malthiery, Y., and Savagner, F. (2010). Estrogen-related receptor alpha and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria. FEBS J 277, 713-725. Moore, R., and Walsh, F.S. (1993). The cell adhesion molecule M-cadherin is specifically expressed in developing and regenerating, but not denervated skeletal muscle. Development 117, 1409-1420. Mootha, V.K., Handschin, C., Arlow, D., Xie, X., St Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., et al. (2004). Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A 101, 6570-6575. Mukai, A., and Hashimoto, N. (2013). Regulation of pre-fusion events: recruitment of M-cadherin to microrafts organized at fusion-competent sites of myogenic cells. BMC Cell Biol 14, 37. Murre, C., McCaw, P.S., Vaessin, H., Caudy, M., Jan, L.Y., Jan, Y.N., Cabrera, C.V., Buskin, J.N., Hauschka, S.D., Lassar, A.B., et al. (1989). Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58, 537-544. Nedachi, T., and Kanzaki, M. (2006). Regulation of glucose transporters by insulin and extracellular glucose in C2C12 myotubes. Am J Physiol Endocrinol Metab 291, E817-828. Neuhold, L.A., and Wold, B. (1993). HLH forced dimers: tethering MyoD to E47 generates a dominant positive myogenic factor insulated from negative regulation by Id. Cell 74, 1033-1042. Nikolic, N., Rhedin, M., Rustan, A.C., Storlien, L., Thoresen, G.H., and Stromstedt, M. (2012). Overexpression of PGC-1alpha increases fatty acid oxidative capacity of human skeletal muscle cells. Biochem Res Int 2012, 714074. Nordgren, M., and Fransen, M. (2014). Peroxisomal metabolism and oxidative stress. Biochimie 98, 56-62. Nordstrom, K., Scholten, I., Nordstrom, J., Larhammar, D., and Miller, D. (2003). Mutational analysis of the Acropora millepora PaxD paired domain highlights the importance of the linker region for DNA binding. Gene 320, 81-87. Numako, C., and Nakai, I. (1995). Xafs Studies of Some Precipitation and Coloration Reaction Used in Analytical-Chemistry. Physica B 208, 387-388. Ow, J.R., Tan, Y.H., Jin, Y., Bahirvani, A.G., and Taneja, R. (2014). Stra13 and Sharp-1, the non-grouchy regulators of development and disease. Curr Top Dev Biol 110, 317-338. Parker, M.H., Perry, R.L., Fauteux, M.C., Berkes, C.A., and Rudnicki, M.A. (2006). MyoD synergizes with the E-protein HEB beta to induce myogenic differentiation. Mol Cell Biol 26, 5771-5783. Puigserver, P., Wu, Z., Park, C.W., Graves, R., Wright, M., and Spiegelman, B.M. (1998). A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829-839. Rome, S., Meugnier, E., Lecomte, V., Berbe, V., Besson, J., Cerutti, C., Pesenti, S., Granjon, A., Disse, E., Clement, K., et al. (2009). Microarray analysis of genes with impaired insulin regulation in the skeletal muscle of type 2 diabetic patients indicates the involvement of basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2). Diabetologia 52, 1899-1912. Rowe, G.C., and Arany, Z. (2014). Genetic models of PGC-1 and glucose metabolism and homeostasis. Rev Endocr Metab Disord 15, 21-29. Salerno, M.S., Thomas, M., Forbes, D., Watson, T., Kambadur, R., and Sharma, M. (2004). Molecular analysis of fiber type-specific expression of murine myostatin promoter. Am J Physiol Cell Physiol 287, C1031-1040. Savagner, F., Mirebeau, D., Jacques, C., Guyetant, S., Morgan, C., Franc, B., Reynier, P., and Malthiery, Y. (2003). PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma. Biochem Biophys Res Commun 310, 779-784. Scarpulla, R.C. (2011). Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 1813, 1269-1278. Schreiber, S.N., Emter, R., Hock, M.B., Knutti, D., Cardenas, J., Podvinec, M., Oakeley, E.J., and Kralli, A. (2004). The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proc Natl Acad Sci U S A 101, 6472-6477. St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J.M., Rhee, J., Jager, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006). Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127, 397-408. St-Pierre, J., Lin, J., Krauss, S., Tarr, P.T., Yang, R., Newgard, C.B., and Spiegelman, B.M. (2003). Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278, 26597-26603. Sun, H., Li, L., Vercherat, C., Gulbagci, N.T., Acharjee, S., Li, J., Chung, T.K., Thin, T.H., and Taneja, R. (2007). Stra13 regulates satellite cell activation by antagonizing Notch signaling. J Cell Biol 177, 647-657. Takeichi, M. (1988). The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development 102, 639-655. Takeshita, S., Suzuki, T., Kitayama, S., Moritani, M., Inoue, H., and Itakura, M. (2012). Bhlhe40, a potential diabetic modifier gene on Dbm1 locus, negatively controls myocyte fatty acid oxidation. Genes Genet Syst 87, 253-264. Valle, I., Alvarez-Barrientos, A., Arza, E., Lamas, S., and Monsalve, M. (2005). PGC-1alpha regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res 66, 562-573. Vega, R.B., Huss, J.M., and Kelly, D.P. (2000). The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20, 1868-1876. Vercherat, C., Chung, T.K., Yalcin, S., Gulbagci, N., Gopinadhan, S., Ghaffari, S., and Taneja, R. (2009). Stra13 regulates oxidative stress mediated skeletal muscle degeneration. Hum Mol Genet 18, 4304-4316. Wheeler, M.T., Snyder, E.C., Patterson, M.N., and Swoap, S.J. (1999). An E-box within the MHC IIB gene is bound by MyoD and is required for gene expression in fast muscle. Am J Physiol 276, C1069-1078. Wolfe, R.R. (1998). Metabolic interactions between glucose and fatty acids in humans. Am J Clin Nutr 67, 519S-526S. Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R.C., et al. (1999). Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124. Yamada, K., and Miyamoto, K. (2005). Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli. Front Biosci 10, 3151-3171. Yun, Z., Maecker, H.L., Johnson, R.S., and Giaccia, A.J. (2002). Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell 2, 331-341. Zephy, D., and Ahmad, J. (2014). Type 2 diabetes mellitus: Role of melatonin and oxidative stress. Diabetes Metab Syndr. Zeschnigk, M., Kozian, D., Kuch, C., Schmoll, M., and Starzinski-Powitz, A. (1995). Involvement of M-cadherin in terminal differentiation of skeletal muscle cells. J Cell Sci 108 ( Pt 9), 2973-2981.
指導教授	陳盛良(Shen-liang Chen)	審核日期	2015-6-17
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