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Ji ZX Du C Wu GS Li SY An GS Yang YX Jia R Jia HT Ni JH 《Molecular genetics and genomics : MGG》2009,281(1):1-10
Although the role of muscle LIM protein (MLP, also known as CRP3), a LIM-only protein of LIM domain-containing protein family,
is well-characterized, the mechanism by which the MLP gene expresses remains unclear. Herein, we demonstrate that myogenin
and myocyte enhancer factor 2C (MEF2C) cooperate in activating the MLP gene in myogenesis. RT-PCR, real-time PCR and Western
blotting showed that overexpression of myogenin or myogenin plus MEF2C led to induction of the MLP gene in differentiating
C2C12 and NIH3T3 fibroblasts. By contrary, knocking-down of myogenin by RNA interference (RNAi) suppressed MLP expression
in differentiating C2C12. Deletion and reporter enzyme assay revealed that the promoter activity was determined largely by
the region extending from −260 to −173, which containing three E-box (CANNTG motif) candidates. Site-directed mutagenesis
demonstrated that the E-box at position −186 to −180 was crucial for activating the promoter by myogenin. Furthermore, MEF2C
could enhance myogenin-mediated activation of the promoter. In addition, chromatin immunoprecipitation (ChIP) and re-ChIP
showed that myogenin and MEF2C were associated with the activated MLP promoter. Together, these results suggest that myogenin
and MEF2C cooperate in the MLP gene activation. The linking of the MLP gene activation with myogenin and MEF2C may facilitate
myogenin-mediated differentiation of striated muscle. 相似文献
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The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD 总被引:12,自引:0,他引:12
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Spiller MP Kambadur R Jeanplong F Thomas M Martyn JK Bass JJ Sharma M 《Molecular and cellular biology》2002,22(20):7066-7082
Myostatin is a negative regulator of myogenesis, and inactivation of myostatin leads to heavy muscle growth. Here we have cloned and characterized the bovine myostatin gene promoter. Alignment of the upstream sequences shows that the myostatin promoter is highly conserved during evolution. Sequence analysis of 1.6 kb of the bovine myostatin gene upstream region revealed that it contains 10 E-box motifs (E1 to E10), arranged in three clusters, and a single MEF2 site. Deletion and mutation analysis of the myostatin gene promoter showed that out of three important E boxes (E3, E4, and E6) of the proximal cluster, E6 plays a significant role in the regulation of a reporter gene in C(2)C(12) cells. We also demonstrate by band shift and chromatin immunoprecipitation assay that the E6 E-box motif binds to MyoD in vitro and in vivo. Furthermore, cotransfection experiments indicate that among the myogenic regulatory factors, MyoD preferentially up-regulates myostatin promoter activity. Since MyoD expression varies during the myoblast cell cycle, we analyzed the myostatin promoter activity in synchronized myoblasts and quiescent "reserve" cells. Our results suggest that myostatin promoter activity is relatively higher during the G(1) phase of the cell cycle, when MyoD expression levels are maximal. However, in the reserve cells, which lack MyoD expression, a significant reduction in the myostatin promoter activity is observed. Taken together, these results suggest that the myostatin gene is a downstream target gene of MyoD. Since the myostatin gene is implicated in controlling G(1)-to-S progression of myoblasts, MyoD could be triggering myoblast withdrawal from the cell cycle by regulating myostatin gene expression. 相似文献
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E-box- and MEF-2-independent muscle-specific expression, positive autoregulation, and cross-activation of the chicken MyoD (CMD1) promoter reveal an indirect regulatory pathway. 总被引:7,自引:1,他引:6
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C A Dechesne Q Wei J Eldridge L Gannoun-Zaki P Millasseau L Bougueleret D Caterina B M Paterson 《Molecular and cellular biology》1994,14(8):5474-5486
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Ayano Naka Kaoruko Tada Iida Yoshimi Nakagawa Hitoshi Iwasaki Yoshinori Takeuchi Aoi Satoh Takashi Matsuzaka Kiyo-aki Ishii Kazuto Kobayashi Shigeru Yatoh Masako Shimada Naoya Yahagi Hiroaki Suzuki Hirohito Sone Nobuhiro Yamada Hitoshi Shimano 《Biochemical and biophysical research communications》2013,430(2):664-669
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S. Watabe 《Journal of fish biology》1999,55(SA):1-18
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