The Mef2c gene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4623-4633 ◽  
Author(s):  
Da-Zhi Wang ◽  
M. Renee Valdez ◽  
John McAnally ◽  
James Richardson ◽  
Eric N. Olson
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Binding Site ◽  
Control Region ◽  
Muscle Development ◽  
Regulatory Elements ◽  
Skeletal Muscle Development ◽  
Helix Loop Helix

Members of the MEF2 family of transcription factors are upregulated during skeletal muscle differentiation and cooperate with the MyoD family of myogenic basic helix-loop-helix (bHLH) transcription factors to control the expression of muscle-specific genes. To determine the mechanisms that regulate MEF2 gene expression during skeletal muscle development, we analyzed the mouse Mef2c gene for cis-regulatory elements that direct expression in the skeletal muscle lineage in vivo. We describe a skeletal muscle-specific control region for Mef2c that is sufficient to direct lacZ reporter gene expression in a pattern that recapitulates that of the endogenous Mef2c gene in skeletal muscle during pre- and postnatal development. This control region is a direct target for the binding of myogenic bHLH and MEF2 proteins. Mutagenesis of the Mef2c control region shows that a binding site for myogenic bHLH proteins is essential for expression at all stages of skeletal muscle development, whereas an adjacent MEF2 binding site is required for maintenance but not for initiation of Mef2c transcription. Our findings reveal the existence of a regulatory circuit between these two classes of transcription factors that induces, amplifies and maintains their expression during skeletal muscle development.

scholarly journals Regulation of Skeletal Muscle Sarcomere Integrity and Postnatal Muscle Function by Mef2c

2007 ◽  
Vol 27 (23) ◽  
pp. 8143-8151 ◽  
Author(s):  
Matthew J. Potthoff ◽  
Michael A. Arnold ◽  
John McAnally ◽  
James A. Richardson ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Muscle Development ◽  
Skeletal Muscle Development ◽  
Postnatal Maturation ◽  
Helix Loop Helix ◽  
Specific Proteins ◽  
Perinatal Lethality ◽  
Bhlh Transcription Factors

ABSTRACT Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skeletal muscle-specific deletion of Mef2c in mice results in disorganized myofibers and perinatal lethality. In contrast, neither Mef2a nor Mef2d is required for normal skeletal muscle development in vivo. Skeletal muscle deficient in Mef2c differentiates and forms normal myofibers during embryogenesis, but myofibers rapidly deteriorate after birth due to disorganized sarcomeres and a loss of integrity of the M line. Microarray analysis of Mef2c null muscles identified several muscle structural genes that depend on MEF2C, including those encoding the M-line-specific proteins myomesin and M protein. We show that MEF2C directly regulates myomesin gene transcription and that loss of Mef2c in skeletal muscle results in improper sarcomere organization. These results reveal a key role for Mef2c in maintenance of sarcomere integrity and postnatal maturation of skeletal muscle.

Effect of kinin B2 receptor ablation on skeletal muscle development and myostatin gene expression

Neuropeptides ◽  
2010 ◽  
Vol 44 (2) ◽  
pp. 209-214 ◽  
Author(s):  
K. de Picoli Souza ◽  
E.C. Batista ◽  
E.D. Silva ◽  
F.C. Reis ◽  
S.M.A. Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Development ◽  
Skeletal Muscle Development ◽  
Myostatin Gene

scholarly journals Deletion of Vitamin D Receptor Gene in Mice Results in Abnormal Skeletal Muscle Development with Deregulated Expression of Myoregulatory Transcription Factors

Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5138-5144 ◽  
Author(s):  
Itsuro Endo ◽  
Daisuke Inoue ◽  
Takao Mitsui ◽  
Yoshifumi Umaki ◽  
Masashi Akaike ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Transcription Factors ◽  
Vitamin D Receptor ◽  
Muscle Development ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Skeletal Muscle Development

scholarly journals Accelerated Response of the myogenin Gene to Denervation in Mutant Mice Lacking Phosphorylation of Myogenin at Threonine 87

2004 ◽  
Vol 24 (5) ◽  
pp. 1983-1989 ◽  
Author(s):  
Chris S. Blagden ◽  
Larry Fromm ◽  
Steven J. Burden
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Electrical Activity ◽  
Muscle Development ◽  
Mutant Mice ◽  
Threonine Residue ◽  
E Boxes ◽  
Bhlh Proteins

ABSTRACT Gene expression in skeletal muscle is regulated by a family of myogenic basic helix-loop-helix (bHLH) proteins. The binding of these bHLH proteins, notably MyoD and myogenin, to E-boxes in their own regulatory regions is blocked by protein kinase C (PKC)-mediated phosphorylation of a single threonine residue in their basic region. Because electrical stimulation increases PKC activity in skeletal muscle, these data have led to an attractive model suggesting that electrical activity suppresses gene expression by stimulating phosphorylation of this critical threonine residue in myogenic bHLH proteins. We show that electrical activity stimulates phosphorylation of myogenin at threonine 87 (T87) in vivo and that calmodulin-dependent kinase II (CaMKII), as well as PKC, catalyzes this reaction in vitro. We find that phosphorylation of myogenin at T87 is dispensable for skeletal muscle development. We show, however, that the decrease in myogenin (myg) expression following innervation is delayed and that the increase in expression following denervation is accelerated in mutant mice lacking phosphorylation of myogenin at T87. These data indicate that two distinct innervation-dependent mechanisms restrain myogenin activity: an inactivation mechanism mediated by phosphorylation of myogenin at T87, and a second, novel regulatory mechanism that regulates myg gene activity independently of T87 phosphorylation.

scholarly journals IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients

2003 ◽  
Vol 163 (5) ◽  
pp. 931-936 ◽  
Author(s):  
Ebru Erbay ◽  
In-Hyun Park ◽  
Paul D. Nuzzi ◽  
Christopher J. Schoenherr ◽  
Jie Chen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Kinase Activity ◽  
Regulatory Elements ◽  
Myoblast Differentiation ◽  
Akt Pathway ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
Primary Target ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGFs) are essential for skeletal muscle development, regeneration, and hypertrophy. Although autocrine actions of IGF-II are known to initiate myoblast differentiation, the regulatory elements and upstream signaling pathways for myogenic expression of IGF-II remain elusive. Here, we report the regulation of IGF-II transcription by mTOR, as well as by amino acid sufficiency, through the IGF-II promoter 3 and a downstream enhancer during C2C12 myoblast differentiation. Furthermore, we present evidence that IGF production, and not IGF signaling, is the primary target for mTOR's function in the initiation of differentiation. Moreover, myogenic signaling by mTOR is independent of its kinase activity and mediated by the PI3K–Akt pathway. Our findings represent the first identification of a signaling pathway that regulates IGF-II expression in myogenesis and implicate the mTOR–IGF axis as a molecular link between nutritional levels and skeletal muscle development.

scholarly journals The Landscape of Chromatin Accessibility in Skeletal Muscle During Embryonic Development in Pigs

2020 ◽  
Author(s):  
Jingwei Yue ◽  
Xinhua Hou ◽  
Xin Liu ◽  
Ligang Wang ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Embryonic Development ◽  
Muscle Development ◽  
Chromatin Accessibility ◽  
Regulatory Role ◽  
Rna Seq ◽  
Skeletal Muscle Development ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development

Abstract Background: The development of skeletal muscle during the embryonic stage in pigs is precisely regulated by transcriptional regulation, which depends on chromatin accessibility. However, how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq on skeletal muscle of pig embryos at 45, 70 and 100 days post coitus (dpc). Results: In total, 21638, 35447 and 60181 unique regions (or peaks) were found across 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100) embryos, respectively. More than 91% of peaks were annotated within -1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from 45 to 100 dpc embryos suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings of integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the peak intensities of ACRs could control the expression of associated genes. Finally, motif screening of stage-specific ACRs revealed some transcription factors that regulated muscle development-related genes, such as MyoD, Mef2c, Mef2d and Pax7. Several potential transcriptional repressors, including E2F6, GRHL2, OTX2 and CTCF, were identified among those genes that exhibited different change trends between the ATAC-seq and RNA-seq data. Conclusions: This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

Integrated analysis of miRNA-mediated ceRNA networks in ovine skeletal muscle development

2020 ◽  
Author(s):  
Tianpei Shi ◽  
Xinyue WANG ◽  
Zhida ZHAO ◽  
Wenping HU ◽  
Li ZHANG
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Muscle Development ◽  
Muscle Growth ◽  
Growth Potential ◽  
Regulatory Role ◽  
Integrated Analysis ◽  
Interaction Patterns ◽  
Rna Seq ◽  
Skeletal Muscle Development

Abstract Background: The embryo stage is a key period for sheep skeletal muscle growth and development. Proliferation, differentiation, and hypertrophy of fibers affect muscle growth potential directly. Analyzing transcriptome data is of great significance for revealing important time nodes of fetus muscle development and screening related regulation factors. Muscle development is a complex biological process, including a intricate network of multiple factor interactions. Among them, non-coding RNA, especially miRNA-mediated regulation, plays a fine regulatory role. The purpose of this study was to investigate the important genes and transcripts involved in the genetic mechanism of embryos skeletal muscle development in late pregnancy. Results: Herein we did a small RNA sequencing(RNA-Seq) of embryo at 85 days (D85N), 105 days (D105N) and 135 days(D135N), then performed bioinformatic analysis in order to identify the miRNA-mediated co-expression networks. Our findings identified 505 DE-miRNAs. Integrating the current miRNA data and the previously obtained lncRNA data, multiple networks were constructed, including miRNA-mRNA, miRNA-target gene(TG)-pathway, lncRNA-miRNA-mRNA, and miRNA-TG-transcription factor (TF) network. The results showed that the miRNA-mRNA network and lncRNA-miRNA-mRNA network identified three important lncRNAs (MSTRG.3533, MSTRG.4324, and MSTRG.1470) and three miRNAs(miR-493-3p, miR-3959-3p and miR-410-5p). The four genes ( TEAD1 , ZBTB34 , GSK3B, and POGLUT1 ) and three transcription factors (C / EBPbeta, TFIID, and PR B) play a key regulatory role in the miRNA-TG-TF network. Notably, a similar trend of gene expression was reported by RT-qPCR for RNA-seq data. Conclusions: This study identified three miRNAs, three lncRNAs, four genes, and three transcription factors, and revealed their crucial role in fetal fibrogenesis and lipid metabolism. It also shows that D105N is a pivotal turning point from myotube differentiation to fiber hypertrophy. These findings provide valuable references for network interaction patterns, which helps to evaluate the biological significance of skeletal muscle in the late development stage.

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