scholarly journals hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

1993 ◽  
Vol 13 (4) ◽  
pp. 2564-2577 ◽  
Author(s):  
J C McDermott ◽  
M C Cardoso ◽  
Y T Yu ◽  
V Andres ◽  
D Leifer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Cortical Neurons ◽  
Myogenic Differentiation ◽  
Mrna Level ◽  
Functional Characterization ◽  
Essential Element ◽  
Specific Pattern ◽  
Cdna Clones ◽  
Tissue Specific

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.

scholarly journals hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors

1993 ◽  
Vol 13 (4) ◽  
pp. 2564-2577
Author(s):  
J C McDermott ◽  
M C Cardoso ◽  
Y T Yu ◽  
V Andres ◽  
D Leifer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Cortical Neurons ◽  
Myogenic Differentiation ◽  
Mrna Level ◽  
Functional Characterization ◽  
Essential Element ◽  
Specific Pattern ◽  
Cdna Clones ◽  
Tissue Specific

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.

scholarly journals Genome-wide identification and expression analysis of bZIP gene family in Carthamus tinctorius L.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haoyang Li ◽  
Lixia Li ◽  
Guodong ShangGuan ◽  
Chang Jia ◽  
Sinan Deng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Functional Characterization ◽  
Draft Genome ◽  
Functional Differentiation ◽  
Regulatory Elements ◽  
Carthamus Tinctorius ◽  
Specific Pattern ◽  
Basic Leucine Zipper ◽  
Protein Motifs ◽  
Genome Wide

Abstract The basic leucine zipper (bZIP) is a widely known transcription factors family in eukaryotes. In plants, the role of bZIP proteins are crucial in various biological functions such as plant growth and development, seed maturation, response to light signal and environmental stress. To date, bZIP protein family has been comprehensively identified in Arabidopsis, castor, rice, ramie, soybean and other plant species, however, the complete genome-wide investigation of Carthamus tinctorius-bZIP family still remains unexplained. Here, we identified 52 putative bZIP genes from Carthamus tinctorius using a draft genome assembly and further analyzed their evolutionary classification, physicochemical properties, Conserved domain analysis, functional differentiation and the investigation of expression level in different tissues. Based on the common bZIP domain, CtbZIP family were clustered into 12 subfamilies renamed as (A–J, S, X), of which the X is a unique subfamily to Carthamus tinctorius. A total of 20 conserved protein motifs were found in CtbZIP proteins. The expression profiling of CtbZIP genes deciphered their tissue-specific pattern. Furthermore, the changes in CtbZIP transcript abundance suggested that their transcription regulation could be highly influenced by light intensity and hormones. Collectively, this study highlights all functional and regulatory elements of bZIP transcription factors family in Carthamus tinctorius which may serve as potential candidates for functional characterization in future.

scholarly journals Zeb2 Regulates Myogenic Differentiation in Pluripotent Stem Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2525
Author(s):  
Ester Sara Di Filippo ◽  
Domiziana Costamagna ◽  
Giorgia Giacomazzi ◽  
Álvaro Cortés-Calabuig ◽  
Agata Stryjewska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Differentiation ◽  
E Box

Skeletal muscle differentiation is triggered by a unique family of myogenic basic helix-loop-helix transcription factors, including MyoD, MRF-4, Myf-5, and Myogenin. These transcription factors bind promoters and distant regulatory regions, including E-box elements, of genes whose expression is restricted to muscle cells. Other E-box binding zinc finger proteins target the same DNA response elements, however, their function in muscle development and regeneration is still unknown. Here, we show that the transcription factor zinc finger E-box-binding homeobox 2 (Zeb2, Sip-1, Zfhx1b) is present in skeletal muscle tissues. We investigate the role of Zeb2 in skeletal muscle differentiation using genetic tools and transgenic mouse embryonic stem cells, together with single-cell RNA-sequencing and in vivo muscle engraftment capability. We show that Zeb2 over-expression has a positive impact on skeletal muscle differentiation in pluripotent stem cells and adult myogenic progenitors. We therefore propose that Zeb2 is a novel myogenic regulator and a possible target for improving skeletal muscle regeneration. The non-neural roles of Zeb2 are poorly understood.

scholarly journals BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dominik Laubscher ◽  
Berkley E. Gryder ◽  
Benjamin D. Sunkel ◽  
Thorkell Andresson ◽  
Marco Wachtel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Target Genes ◽  
De Novo ◽  
Fusion Gene ◽  
Myogenic Differentiation ◽  
Complex Function ◽  
Genome Wide ◽  
Myogenic Program

AbstractRhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters the myogenic program and maintains the proliferative state while blocking terminal differentiation. Here, we investigated the contributions of chromatin regulatory complexes to FP-RMS tumor maintenance. We define the mSWI/SNF functional repertoire in FP-RMS. We find that SMARCA4 (encoding BRG1) is overexpressed in this malignancy compared to skeletal muscle and is essential for cell proliferation. Proteomic studies suggest proximity between PAX3-FOXO1 and BAF complexes, which is further supported by genome-wide binding profiles revealing enhancer colocalization of BAF with core regulatory transcription factors. Further, mSWI/SNF complexes localize to sites of de novo histone acetylation. Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes, which is recapitulated by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor.

scholarly journals BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma

2021 ◽  
Author(s):  
Dominik Laubscher ◽  
Berkley Gryder ◽  
Benjamin Sunkel ◽  
Thorkell Andresson ◽  
Sudipto Das ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Target Genes ◽  
De Novo ◽  
Fusion Gene ◽  
Myogenic Differentiation ◽  
Complex Function ◽  
Genome Wide ◽  
Myogenic Program

Abstract Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters the myogenic program and maintains the proliferative state wile blocking terminal differentiation. Here we investigated the contributions of chromatin regulatory complexes to FP-RMS tumor maintenance. We define, for the first time, the mSWI/SNF repertoire in FP-RMS. We find that SMARCA4 (encoding BRG1) is overexpressed in this malignancy compared to skeletal muscle and is essential for cell proliferation. Proteomic studies suggest proximity between PAX3-FOXO1 and BAF complexes, which is further supported by genome-wide binding profiles revealing enhancer colocalization of BAF with core regulatory transcription factors. Further, mSWI/SNF complexes act as sensors of chromatin state and are recruited to sites of de novo histone acetylation. Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes which is reproduced by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor.

scholarly journals Sharp-1/DEC2 Inhibits Skeletal Muscle Differentiation through Repression of Myogenic Transcription Factors

2004 ◽  
Vol 279 (50) ◽  
pp. 52643-52652 ◽  
Author(s):  
Sameena Azmi ◽  
Anne Ozog ◽  
Reshma Taneja
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Myogenic Differentiation ◽  
Constitutive Expression ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
E Proteins ◽  
C2c12 Myoblasts ◽  
E Box ◽  
Bhlh Factors

Skeletal muscle differentiation is regulated by the basic-helix-loop-helix (bHLH) family of transcription factors. The myogenic bHLH factors form heterodimers with the ubiquitously expressed bHLH E-proteins and bind E-box (CANNTG) sites present in the promoters of several muscle-specific genes. Our previous studies have shown that the bHLH factor Sharp-1 is expressed in skeletal muscle and interacts with MyoD and E-proteins. However, its role in regulation of myogenic differentiation remains unknown. We report here that endogenous Sharp-1 is expressed in proliferating C2C12 myoblasts and is down-regulated during myogenic differentiation. Constitutive expression of Sharp-1 in C2C12 myoblasts promotes cell cycle exit causing a decrease in cyclin D1 expression but blocks terminal differentiation. Although MyoD expression is not inhibited, the induction of differentiation-specific genes such as myogenin, MEF2C, and myosin heavy chain is impaired by Sharp-1 overexpression. We demonstrate that the interaction of Sharp-1 with MyoD and E-proteins results in reduced DNA binding and transactivation from MyoD-dependent E-box sites. Re-expression of MyoD∼E47 rescues the differentiation defect imposed by Sharp-1, suggesting that myogenic bHLH factors function downstream of Sharp-1. Our data suggest that protein-protein interactions between Sharp-1, MyoD, and E47 resulting in interference with MyoD function underlies Sharp-1-mediated repression of myogenic differentiation.

scholarly journals Actin-related protein 5 functions as a novel modulator of MyoD and MyoG in skeletal muscle and in rhabdomyosarcoma

2021 ◽  
Author(s):  
Tsuyoshi Morita ◽  
Ken'ichiro Hayashi
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Chromatin Remodeling ◽  
Myogenic Differentiation ◽  
Related Protein ◽  
Chromatin Remodelers ◽  
Hind Limbs ◽  
Muscle Tissues ◽  
Extension Class

Myogenic regulatory factors (MRFs) are pivotal transcription factors in myogenic differentiation. MyoD commits cells to the skeletal muscle lineage by inducing myogenic genes through recruitment of chromatin remodelers to its target loci. This study showed that Actin-related protein 5 (Arp5) acts as an inhibitory regulator of MyoD and MyoG by binding to their cysteine-rich (CR) region, which overlaps with the region essential for their epigenetic functions. Arp5 expression was faint in skeletal muscle tissues. Excessive Arp5 in mouse hind limbs caused skeletal muscle fiber atrophy. Further, Arp5 overexpression in myoblasts inhibited myotube formation by diminishing myogenic gene expression, whereas Arp5 depletion augmented myogenic gene expression. Arp5 disturbed MyoD-mediated chromatin remodeling through competition with the three-amino-acid-loop-extension-class homeodomain transcription factors the Pbx1–Meis1 heterodimer for binding to the CR region. This antimyogenic function was independent of the INO80 chromatin remodeling complex, although Arp5 is an important component of that. In rhabdomyosarcoma (RMS) cells, Arp5 expression was significantly higher than in normal myoblasts and skeletal muscle tissue, probably contributing to MyoD and MyoG activity dysregulation. Arp5 depletion in RMS partially restored myogenic properties while inhibiting tumorigenic properties. Thus, Arp5 is a novel modulator of MRFs in skeletal muscle differentiation.

Molecular Basis of Skeletal Muscle Regeneration

1996 ◽  
Vol 21 (3) ◽  
pp. 155-184 ◽  
Author(s):  
Rebecca L. Chambers ◽  
John C. McDermott
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Growth Factors ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Regulatory Sequences ◽  
Nuclear Factors ◽  
Dna Regulatory Sequences

Skeletal muscle regeneration is a vital process with important implications for various muscle myopathies and adaptations to physiological overload. Few of the molecular regulatory proteins controlling this process have so far been identified. Several growth factors have defined effects on myogenic precursor cells and appear to also be involved during regeneration. In addition, factors that may be released by cells of the immune system may activate satellite cells during regeneration. Many of these growth factors are associated with signalling cascades which transmit information to the nucleus. The nuclear "receptors" that receive the incoming signals are transcription factors that interact with DNA regulatory sequences in order to modulate gene expression. Of the nuclear factors isolated so far, the immediate-early genes are associated with muscle precursor cell proliferation. This review aims to synthesize the extensive research on myogenic differentiation and relate this to research concerning the molecular regulation of skeletal muscle regeneration. Key words: satellite cells, growth factors, signal transduction, transcription factors, gene regulation, overload adaptation

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