Complex regulation of the muscle-specific contractile protein (troponin I) gene.

Konieczny, Stephen F.; Emerson, Charles P.

doi:10.1128/mcb.7.9.3065

Cited by 103 publications

(65 citation statements)

References 57 publications

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“…This structure is present in both Drosophila (Basi and Storti, 1986;Falkenthal et al, 1984;Geyer and Fyrberg, 1986;Marin et al, 2004;Mas et al, 2004;Parker et al, 1985) and vertebrate muscle genes (Baldwin et al, 1985;Chang et al, 1985;Fornwald et al, 1982;Nabeshima et al, 1984;Strehler et al, 1986). Transcriptional enhancer elements are located in the first intron of a number of such muscle genes (Konieczny and Emerson, 1987;Marin et al, 2004;Mas et al, 2004;Meredith and Storti, 1993;Ng et al, 1989;Yutzey et al, 1989). …”

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Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Hess

Singer

Trinh

et al. 2007

Gene Expression Patterns

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We show that a 2.6 kb fragment of the muscle myosin heavy-chain gene (Mhc) of Drosophila melanogaster (containing 458 base pairs of upstream sequence, the first exon, the first intron and the beginning of the second exon) drives expression in all muscles. Comparison of the minimal promoter to Mhc genes of ten Drosophila species identified putative regulatory elements in the upstream region and in the first intron. The first intron is required for expression in four small cells of the tergal depressor of the trochanter (jump) muscle and in the indirect flight muscle. The 3′ end of this intron is important for Mhc transcription in embryonic body wall muscle and contains AT-rich elements that are protected from DNase I digestion by nuclear proteins of Drosophila embryos. Sequences responsible for expression in embryonic, adult body wall and adult head muscles are present both within and outside the intron. Elements important for expression in leg muscles and in the large cells of the jump muscle flank the intron. We conclude that multiple transcriptional regulatory elements are responsible for Mhc expression in specific sets of Drosophila muscles. KeywordsDrosophila melanogaster; muscle; myosin heavy chain; transcription; enhancer; gene regulation Drosophila melanogaster is unusual in having a single muscle myosin heavy-chain gene (Mhc) (Bernstein et al., 1983;Rozek and Davidson, 1983), rather than a Mhc multigene family (see Emerson and Bernstein, 1987 for review). Alternative splicing of the primary transcripts from this gene yields multiple isoforms of the protein (Collier et al., 1990;George et al., 1989;Hastings and Emerson, 1991;Kazzaz and Rozek, 1989;Kronert et al., 1991;Zhang and Bernstein, 2001). Drosophila Mhc is expressed in all muscles at embryonic, larval, pupal and adult stages. Thus several stage-or muscle-specific enhancer elements may regulate its transcription.Transcriptional regulatory regions for a number of Drosophila muscle genes have been mapped, resulting in the identification of both unique and shared cis-acting elements (Arredondo et al., 2001;Kelly et al., 2002;Marin et al., 2004;Mas et al., 2004;Meredith and Storti, 1993). The latter includes E-boxes that bind helix-loop-helix transcription factors and MEF2 sites that bind MEF2 protein (Bour et al., 1995; Lilly et al., 1995). E-boxes, MEF2 sites and their binding factors positively regulate vertebrate muscle gene expression as well (see Molkentin and Olson, 1996 for review).* Corresponding author. Tel.: +1-619-594-5629; fax: +1-619-594-5676; E-mail address: sbernst@sunstroke.sdsu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal dis...

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Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Hess

Singer

Trinh

et al. 2007

Gene Expression Patterns

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“…Towards this end we have analyzed the promoter region of the gene encoding the fast isoform of skeletal troponin I (sTnI). The sTnI gene is an ideal choice for such a study because previous work has shown that the first intron of this gene contains a strong muscle-specific enhancer (29,58). Here we show that the sTnI promoter also contains elements which restrict expression to skeletal muscle cells, and by using deletion, chimeric promoter, and footprint analyses we localized the essential regulatory elements to two components, one located upstream and one downstream of the transcription initiation site.…”

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confidence: 97%

“…One such motif, 5'-CC(A+T rich)6GG-3' (CArG/CBAR motif) is located in multiple copies upstream of the transcription initiation sites of sarcomeric actin genes (5, 41) and has been shown to be required for the muscle-specific expression of sarcomeric actin genes in a number of diverse species (5, 41-43). A second conserved, variable sequence motif, dubbed MEF-1, has been shown to be an essential component of the muscle-specific enhancer of the creatine kinase gene (7) and may be an essential component of the enhancers of other muscle-specific genes (11,58 (29,58). Here we show that the sTnI promoter also contains elements which restrict expression to skeletal muscle cells, and by using deletion, chimeric promoter, and footprint analyses we localized the essential regulatory elements to two components, one located upstream and one downstream of the transcription initiation site.…”

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Muscle-specific activity of the skeletal troponin I promoter requires interaction between upstream regulatory sequences and elements contained within the first transcribed exon.

Nikovits¹,

Mar²,

Ordahl³

1990

Mol. Cell. Biol.

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Expression of the skeletal troponin I (sTnI) gene is regulated transcriptionally in a muscle-specific fashion. We show here that the region of the sTnI gene between -160 and +61 (relative to the transcription initiation site) is able to direct expression of the bacterial chloramphenicol acetyltransferase (CAT) During development of skeletal muscle, specific isoforms of the contractile proteins accumulate in the cytoplasm, where they become assembled into myofilaments. The mRNAs which encode these muscle-specific isoforms of the contractile proteins begin to accumulate during terminal differentiation, when proliferating myoblasts withdraw from the cell cycle and fuse to form multinucleated myotubes (10,24). Thus, coexpression of many unlinked genes occurs during differentiation to produce the skeletal muscle phenotype. How expression of this gene set is regulated is a fundamental question in muscle development. One approach to this question is to identify and compare the cis elements responsible for muscle-specific activity within individual muscle genes.At least three different regulatory elements have been identified which appear to be important in governing the cell-specific expression of individual muscle-specific genes. One such motif, 5'-CC(A+T rich)6GG-3' (CArG/CBAR motif) is located in multiple copies upstream of the transcription initiation sites of sarcomeric actin genes (5, 41) and has been shown to be required for the muscle-specific expression of sarcomeric actin genes in a number of diverse species (5, 41-43). A second conserved, variable sequence motif, dubbed MEF-1, has been shown to be an essential component of the muscle-specific enhancer of the creatine kinase gene (7) and may be an essential component of the enhancers of other muscle-specific genes (11,58 (29,58). Here we show that the sTnI promoter also contains elements which restrict expression to skeletal muscle cells, and by using deletion, chimeric promoter, and footprint analyses we localized the essential regulatory elements to two components, one located upstream and one downstream of the transcription initiation site. Thus, our results show that, for the sTnI gene, musclespecific expression is governed by a complex interaction between multiple elements located both in the promoter and in the intragenic regions.

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“…trans-Acting, tissue-specific regulatory factors which may interact with such elements have been identified by a combination of molecular (17), biochemical (41), and cell biological approaches (8,22). In most biological systems, complexities and incongruities in the tissue-specific regulation of gene expression suggest a hierarchy of control steps which to date remain unresolved (26,28,36,53).Muscle is an ideal system with which to study molecular differentiation in vitro. Mononucleate myoblasts from primary cultures or established cell lines can be propagated in the undifferentiated state under conditions of high serum and low cell density.…”

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“…At the genomic level, several types of cis-acting DNA sequences which regulate gene expression in a tissue-specific manner have been characterized (14,28,36). trans-Acting, tissue-specific regulatory factors which may interact with such elements have been identified by a combination of molecular (17), biochemical (41), and cell biological approaches (8,22).…”

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Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation.

Akhurst¹,

Flavin²,

Worden³

1988

Mol. Cell. Biol.

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A new variant rat myogenic cell line, ts485, was isolated by subcloning the cell line ts3b2 (H. T. Nguyen, R. M. Medford, and B. Nadal-Ginard, Cell 34:281-293, 1983). Unlike the progenitor cell line, ts485 was thermosensitive for differentiation. Experiments with conditioned medium suggested that diffusible extracellular factors were not involved in dictating the differential phenotypes of ts485 cells cultured at the permissive and nonpermissive temperatures. Temperature shift experiments performed on cultures of ts485 cells indicated that the temperature-sensitive lesion was in a factor active during the growth phase and required to trigger a cascade of events leading to terminal differentiation.Our understanding of the molecular control of gene expression during cellular differentiation is still superficial despite efforts with multiple experimental approaches. At the genomic level, several types of cis-acting DNA sequences which regulate gene expression in a tissue-specific manner have been characterized (14,28,36). trans-Acting, tissue-specific regulatory factors which may interact with such elements have been identified by a combination of molecular (17), biochemical (41), and cell biological approaches (8,22). In most biological systems, complexities and incongruities in the tissue-specific regulation of gene expression suggest a hierarchy of control steps which to date remain unresolved (26,28,36,53).Muscle is an ideal system with which to study molecular differentiation in vitro. Mononucleate myoblasts from primary cultures or established cell lines can be propagated in the undifferentiated state under conditions of high serum and low cell density. After removal of mitogens from the medium, the cells will align, differentiate, and fuse to form multinucleate myotubes. The muscle-specific genes encoding contractile proteins, cell surface receptors, and energygenerating enzymes are coordinately activated during this process (10,23,48). By experimental manipulation, myogenesis has been dissected into sequential stages, beginning with withdrawal from the cell cycle at Gl. This is followed by muscle-specific gene activation, commitment to terminal differentiation, and cell fusion (37, 40). Each step can be studied independently with biological inhibitors of the various processes of myogenesis (3,15,31,39,46).Identification of conditional myoblast mutants temperature sensitive for various stages of myogenesis has allowed further characterization of the sequential events of myogenesis at the morphological and biochemical levels (30, 40). The rat myoblast line ts3b2, in particular, has been extensively studied with respect to its temperature-sensitive phenotype for commitment to terminal differentiation (39, 40). The availability of other temperature-sensitive cell lines defective for various stages of myogenesis would not only provide models to probe the mechanisms regulating differentiation but could also provide the potential to isolate specific regulatory genes by DNA complementation.Here we report the isolat...

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Complex regulation of the muscle-specific contractile protein (troponin I) gene.

Cited by 103 publications

References 57 publications

Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

Muscle-specific activity of the skeletal troponin I promoter requires interaction between upstream regulatory sequences and elements contained within the first transcribed exon.

Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation.

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