Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation

2010 ◽  
Vol 428 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Xiaozhong Shi ◽  
Daniel J. Garry
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Development ◽  
Cellular Proliferation ◽  
Elongation Factor ◽  
Muscle Differentiation ◽  
Myogenic Regulatory Factors ◽  
Mobility Shift ◽  
Regulatory Factors ◽  
E Box

Recurrent injuries eventually exhaust the capacity of skeletal muscle to fully restore or regenerate its cellular architecture. Therefore a comprehensive understanding of the muscle regeneration programme is needed to provide a platform for new therapies for devastating diseases such as Duchenne muscular dystrophy. To begin to decipher the molecular programme that directs muscle regeneration, we undertook an unbiased strategy using microarray analysis of cardiotoxin-injured skeletal muscle at defined time periods in the adult mouse. Using this strategy, we identified Tceal7 [transcription elongation factor A (SII)-like 7], which was dynamically regulated during muscle regeneration. Our studies revealed that Tceal7 was restricted to the skeletal muscle lineage during embryogenesis. Using transgenic technologies and transcriptional assays, we defined an upstream 0.7 kb fragment of the Tceal7 gene that directed the LacZ reporter to the developing skeletal muscle lineage. Analysis of the Tceal7 promoter revealed evolutionarily conserved E-box motifs within the 0.7 kb upstream fragment that were essential for promoter activity, as mutation of the E-box motifs resulted in the loss of reporter expression in the somites of transgenic embryos. Furthermore, we demonstrated that MRFs (myogenic regulatory factors) were Tceal7 upstream transactivators using transcriptional assays, EMSAs (electrophoretic mobility-shift assays), and ChIP (chromatin immunoprecipitation) assays. Overexpression of Tceal7 in C2C12 myoblasts decreased cellular proliferation and enhanced differentiation. Further studies revealed that p27 expression was up-regulated following Tceal7 overexpression. These studies support the hypothesis that MRFs transactivate Tceal7 gene expression and promote muscle differentiation during muscle development and regeneration.

scholarly journals OR-009 The expression and roles of lncRNAs in the regeneration of skeletal muscle contusion

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lifang Zheng ◽  
Peijie Chen ◽  
Weihua Xiao
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Control Group ◽  
Myogenic Regulatory Factors ◽  
Post Injury ◽  
Regulatory Factors ◽  
Expression Levels ◽  
Skeletal Muscle Contusion

Objective In recent years, Accumulating evidence from myoblast differentiation in vitro, cardiotoxin (CTX)-mediated injury or mdx mice suggested that some lncRNAs such as Malat1, H19, linc-MD1, linc-YY1, Sirt1 AS and lnc-mg may modulate myogenesis and muscle regeneration. However, the change of lncRNAs in skeletal muscle contusion and their possible roles are still unclear. We hypothesize that the lncRNAs may be involved in the repair of skeletal muscle contusion. Methods Forty C57BL/6 male mice were randomly divided into two groups, uninjured control group (group C) and muscle contusion group (group S). The mice of group S suffered from contusion injury. All the mice were killed to harvest gastrocnemius at 3, 6, 12 and 24 days post-injury. The gene expression were detected by PCR technique. Gastrocnemius were stained with H & E to evaluate the general morphology. Data were analyzed by One-way analysis of variance, with statistical significance being set at p ≤ 0.05. Results The expression levels of linc-MD1 and Sirt1 AS were significantly higher than that of the uninjured control group at 3, 6 and 12 days post-injury (p<0.01). And Malat1 was highly expressed in the skeletal muscle of the muscle contusion group at 3 days post-injury and continuously up-regulated at 6 days (p<0.01). Moreover, linc-YY1 and H19 were all elevated significantly at 6 days (all p<0.01), but their gene expression levels did not change significantly at 3, 12 and 24 days post-injury, as compared to the uninjured control group. Furthermore, lnc-mg mRNA level did not change significantly in the whole process of regeneration after muscle contusion except the time point of 12 days post-injury which decreased significantly (p<0.01). The expression of myogenic regulatory factors (MyoD, myogenin, myf5, myf6) were studied, they were all elevated significantly at 3 and 6 days (all p<0.01; except myogenin ), and returned to normal at 24 days post-injury, as compared to the uninjured control group. Meanwhile, Pearson correlations showed that there was an correlation between lincRNAs and myogenic regulatory factors mentioned above. Conclusions The expression of myogenic regulatory factors increased significantly after muscle contusion. Meanwhile, varieties of lncRNAs (Malat1, H19, lnc-mg, linc-MD1, linc-YY1, Sirt1 AS) were also up-regulated. Moreover, there was correlation between lncRNAs and myogenic regulatory factors for skeletal muscle regeneration. These results suggest that lncRNAs may play important roles in the regeneration of skeletal muscle contusion.

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

1997 ◽  
Vol 83 (4) ◽  
pp. 1270-1275 ◽  
Author(s):  
Daniel R. Marsh ◽  
David S. Criswell ◽  
James A. Carson ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Young Adult ◽  
Muscle Regeneration ◽  
Tibialis Anterior Muscle ◽  
Brown Norway ◽  
Mrna Levels ◽  
Myogenic Regulatory Factors ◽  
Adult Rats ◽  
Regulatory Factors ◽  
Old Rats

Marsh, Daniel R., David S. Criswell, James A. Carson, and Frank W. Booth. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270–1275, 1997.—Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

scholarly journals Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

2020 ◽  
Author(s):  
Gist H. Farr ◽  
Bingsi Li ◽  
Maurizio Risolino ◽  
Nathan M. Johnson ◽  
Zizhen Yao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Muscle Differentiation ◽  
Mouse Embryos ◽  
Fast Muscle ◽  
Fiber Types ◽  
Skeletal Muscle Differentiation ◽  
Homeodomain Proteins ◽  
Evolutionarily Conserved ◽  
Fast Twitch

SummaryVertebrate skeletal muscles are composed of both slow-twitch and fast-twitch fiber types. How the differentiation of distinct fiber types is activated during embryogenesis is not well characterized. Skeletal muscle differentiation is initiated by the activity of the myogenic basic helix-loop-helix (bHLH) transcription factors Myf5, Myod1, Myf6, and Myog. Myod1 functions as a muscle master regulatory factor and directly activates muscle differentiation genes, including those specific to both slow and fast muscle fibers. Our previous studies showed that Pbx TALE-class homeodomain proteins bind with Myod1 on the promoter of the zebrafish fast muscle gene mylpfa and are required for proper activation of mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Pbx proteins have also been shown to bind regulatory regions of muscle differentiation genes in mammalian muscle cells in culture. Here, we use new zebrafish mutant strains to confirm the essential roles of zebrafish Pbx factors in embryonic fast muscle differentiation. Furthermore, we examine the requirements for Pbx genes in mouse embryonic skeletal muscle differentiation, an area that has not been investigated in the mammalian embryo. Removing Pbx1 function from skeletal muscle in Myf5Cre/+;Pbx1fl/fl mouse embryos has minor effects on embryonic muscle development. However, concomitantly deleting Pbx2 function in Myf5Cre/+;Pbx1fl/fl;Pbx2-/- mouse embryos causes delayed activation and reduced expression of fast muscle differentiation genes. In the mouse, Pbx1/Pbx2-dependent fast muscle genes closely match those that have been previously shown to be dependent on murine Six1 and Six4. This work establishes evolutionarily conserved requirements for Pbx factors in embryonic fast muscle differentiation. Our studies are revealing how Pbx homeodomain proteins help direct specific cellular differentiation pathways.

scholarly journals MiR-27b Promotes Muscle Development by Inhibiting MDFI Expression

2018 ◽  
Vol 46 (6) ◽  
pp. 2271-2283 ◽  
Author(s):  
Lianjie Hou ◽  
Jian Xu ◽  
Yiren Jiao ◽  
Huaqin Li ◽  
Zhicheng Pan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Western Blot ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Target Gene ◽  
Muscle Development ◽  
Muscle Satellite Cells ◽  
Qrt Pcr

Background/Aims: Skeletal muscle plays an essential role in the body movement. However, injuries to the skeletal muscle are common. Lifelong maintenance of skeletal muscle function largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation, differentiation, and myoblast fusion play an important role in muscle regeneration after injury. Therefore, understanding of the mechanisms associated with muscle development during muscle regeneration is essential for devising the alternative treatments for muscle injury in the future. Methods: Edu staining, qRT-PCR and western blot were used to evaluate the miR-27b effects on pig muscle satellite cells (PSCs) proliferation and differentiation in vitro. Then, we used bioinformatics analysis and dual-luciferase reporter assay to predict and confirm the miR-27b target gene. Finally, we elucidate the target gene function on muscle development in vitro and in vivo through Edu staining, qRT-PCR, western blot, H&E staining and morphological observation. Result: miR-27b inhibits PSCs proliferation and promotes PSCs differentiation. And the miR-27b target gene, MDFI, promotes PSCs proliferation and inhibits PSCs differentiation in vitro. Furthermore, interfering MDFI expression promotes mice muscle regeneration after injury. Conclusion: our results conclude that miR-27b promotes PSCs myogenesis by targeting MDFI. These results expand our understanding of muscle development mechanism in which miRNAs and genes work collaboratively in regulating skeletal muscle development. Furthermore, this finding has implications for obtaining the alternative treatments for patients with the muscle injury.

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