The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements.

Horlick, R A; Benfield, P A

doi:10.1128/mcb.9.6.2396

Cited by 90 publications

(99 citation statements)

References 48 publications

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“…In addition, there was diminished DNA binding activity of the muscle-specific transcription factor MEF-2. These data and other experimental evidence indicate that MEF-2 is involved in the activation of muscle-specific genes, including rat myosin light chain 2 slow, human myoglobin, rat muscle creatine kinase, mouse troponin C slow, and human beta enolase (14,15,20,26,50). In addition, MEF-2 has been proposed to serve as a nodal point in the mechanisms by which motor nerves control the program of gene expression in skeletal muscle fibers and in the pathway leading to cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 86%

Myocyte Enhancer Factor 2 Activates Promoter Sequences of the Human AβH-J-J Locus, Encoding Aspartyl-β-Hydroxylase, Junctin, and Junctate

Feriotto

Finotti²,

Volpe

et al. 2005

Molecular and Cellular Biology

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Alternative splicing of the locus A␤H-J-J generates three functionally distinct proteins: an enzyme, A␤H (aspartyl-␤-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Junctin and junctate are two important proteins involved in calcium regulation in eukaryotic cells. To understand the regulation of these two proteins, we identified and functionally characterized one of the two promoter sequences of the A␤H-J-J locus. We demonstrate that the P2 promoter of the A␤H-J-J locus contains (i) a minimal sequence localized within a region ؊159 bp from the transcription initiation site, which is sufficient to activate transcription of both mRNAs; (ii) sequences which bind known transcriptional factors such as those belonging to the myocyte enhancer factor 2 (MEF-2), MEF-3, and NF-B protein families; and (iii) sequences bound by unknown proteins. The functional characterization of the minimal promoter in C2C12 cells and in the rat soleus muscle in vivo model indicates the existence of cis elements having positive and negative effects on transcription. In addition, our data demonstrate that in striated muscle cells the calcium-dependent transcription factor MEF-2 is crucial for the transcription activity directed by the P2 promoter. The transcription directed by the A␤H-J-J P2 promoter is induced by high expression of MEF-2, further stimulated by calcineurin and Ca2 ؉ /calmodulindependent protein kinase I, and inhibited by histone deacetylase 4.

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Section: Discussionmentioning

confidence: 86%

Myocyte Enhancer Factor 2 Activates Promoter Sequences of the Human AβH-J-J Locus, Encoding Aspartyl-β-Hydroxylase, Junctin, and Junctate

Feriotto

Finotti²,

Volpe

et al. 2005

Molecular and Cellular Biology

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“…In addition, the combination of the MCK enhancer and the 1-kb region produces greater activity in both thigh and cardiac muscle than does either region alone (16). To further delineate the active portions of the 1-kb region, we compared mouse, rat, rabbit, and human MCK sequences (27,31,65,73) to determine which portions were most highly conserved. The first 358 bp of the 5Ј region exhibited more than 50% sequence similarity, whereas there was little similarity between bp Ϫ1049 and Ϫ359.…”

Section: Resultsmentioning

confidence: 99%

“…The 5Ј MCK enhancer contains a number of sequence motifs-including the E box, CArG, and AT-rich sites-which are recognized by tissue-specific and ubiquitous transcription factors. Mutational analysis of these sites showed that several are critical for activity in cultured skeletal and cardiac muscle (1,7,21,27); however, the mutations had different effects when tested in transgenic mice (16). Mutation of the Right E box, which is a target for basic-helix-loop-helix (bHLH) DNA-binding factors (17,48,69) such as the myogenic factors MyoD and myogenin and the ubiquitous bHLH factors E12/E47 and E2-2 (2,40,45), caused a nearly 100-fold reduction in expression in transfected skeletal muscle cells and a 6-fold decrease in expression in transiently transfected cardiomyocytes (1,7).…”

mentioning

confidence: 99%

E-Box Sites and a Proximal Regulatory Region of the Muscle Creatine Kinase Gene Differentially Regulate Expression in Diverse Skeletal Muscles and Cardiac Muscle of Transgenic Mice

Shield

Haugen

Clegg

et al. 1996

Molecular and Cellular Biology

106

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Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse muscle differed from those required in cell culture, suggesting that distinct modes of muscle gene regulation occur in vivo. To examine this further, we measured the activity of MCK transgenes containing E-box and promoter deletions in a variety of striated muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5 region, which abolished transcription in muscle cultures, had strikingly different effects in mice. The mutations abolished transgene expression in cardiac and tongue muscle and caused a reduction in expression in the soleus muscle (a muscle with many slow fibers) but did not affect expression in predominantly fast muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory sequences with muscle-type-specific activities were found within the 358-bp 5-flanking region. This proximal region conferred relatively strong expression in limb and abdominal skeletal muscles but was inactive in cardiac and tongue muscles. However, when the 206-bp 5 enhancer was ligated to the 358-bp region, high levels of tissue-specific expression were restored in all muscle types. These results indicate that E boxes and a proximal regulatory region are differentially required for maximal MCK transgene expression in different striated muscles. The overall results also imply that within skeletal muscles, the steady-state expression of the MCK gene and possibly other muscle genes depends on transcriptional mechanisms that differ between fast and slow fibers as well as between the anatomical and physiological attributes of each specific muscle.Creatine kinase catalyzes the regeneration of ATP from creatine phosphate and provides energy for contraction in all striated muscle types. The muscle creatine kinase (MCK) gene is transcriptionally activated during differentiation of myoblasts to myocytes (8, 31) and encodes the predominant creatine kinase isoform expressed in mammalian skeletal and cardiac muscle. While it seems likely that intrinsic differences in striated muscle anatomy and physiology would affect MCK gene expression, little is known concerning the steady-state mechanisms of MCK transcription in diverse muscle types. This transgenic study seeks to identify regulatory regions and elements within the MCK gene that are involved in controlling muscle-type-specific expression.Several regions within the mouse MCK gene 5Ј-flanking sequence are required for muscle-specific expression in cultured myocytes and cardiomyocytes (1, 32, 64). Of particular interest is a 206-bp enhancer located approximately 1 kb upstream of the transcription start site. This region functions in an orientation-independent manner and drives the expression of heterologous promoters in skeletal myocytes (32). The 5Ј MCK enhancer contains a number of sequence motifs-including the E box, CArG, and AT-rich sites-which are recognized by tissue-specific and ubiquitous transcription factors. Mutation...

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“…These binding sites contribute to the in vivo activity of the MCK (Gossett et al 1989;Horlick and Benfield 1989) and m y o s i n light-chain 1/3 (Donoghue et al 1988;Wentworth et al 1991) gene enhancers, and the myosin light-chain type 2A (Braun et al 1989;Zhu et al 1991) and creatine kinase B (Hobson et al 1988 promoters. These sites have been shown 2C) were inserted into pBLCAT2, and the resulting plasmids were transfected into NIH-3T3 cells.…”

Section: Potential Target Promoters For Rsrf Proteinsmentioning

confidence: 99%

“…One, from the promoter of the cellular immediate early gene N10 (Hazel et al 1988;Changelian et al 1989;Ryseck et al 1989), represents an example of the most common sequence recovered in the site selection CTATT-TATAG. The second, from the muscle-specific creatine kinase (MCK) gene enhancer, represents a variant site, CTAAAAATAA, identified previously as a functional element and factor-binding site in this enhancer (Gossett et al 1989;Horlick and Benfield 1989;Mueller and Wold 1989;Horlick et al 1990). …”

Section: Interaction Of Rsrfc4 With Natural Cta(t/a)4tag Elementsmentioning

confidence: 99%

Human SRF-related proteins: DNA-binding properties and potential regulatory targets.

Pollock¹,

Treisman²

1991

Genes & Development

423

470

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Serum response factor (SRF) is a transcription factor that binds the sequence CC(A/T)6GG found in a number of growth factor-inducible and muscle-specific promoters. We describe the isolation and characterization of cDNA clones encoding a family of three human SRF-related DNA-binding proteins. Each of these RSRF (related to SRF) proteins contains an 86-amino-acid amino-terminal region related to the SRF DNA-binding domain: In RSRFC4 and RSRFC9, this region is identical, whereas that present in RSRFR2 differs by seven conservative amino acid substitutions. The DNA-binding specificity of the RSRF proteins, which recognize the consensus sequence CTA(A/T)4TAG, is distinct from that of SRF. The entire RSRF common region is required for DNA binding, and the differential sequence specificity of the RSRFs and SRF is the result of differences in the basic amino-terminal part of this domain. The RSRF proteins bind DNA as dimers and can dimerize with one another but not with SRF. Although the RSRF mRNAs are expressed in many cell types, RSRFR2 mRNA is expressed at elevated levels in several B-cell lines. Consistent with this, extracts from many cell types form CTA(A/T)4TAG-binding complexes that contain RSRF proteins, and oligonucleotides containing RSRF-binding sites function as promoter elements in transfection assays. Like SRF-binding sites, RSRF-binding sites are found in the regulatory sequences of a number of growth factor-inducible and muscle-specific genes, and we show that RSRF polypeptides are components of previously characterized binding activities that interact with these elements. We discuss the potential role of RSRF proteins in the regulation of these genes.

show abstract

The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements.

Cited by 90 publications

References 48 publications

Myocyte Enhancer Factor 2 Activates Promoter Sequences of the Human AβH-J-J Locus, Encoding Aspartyl-β-Hydroxylase, Junctin, and Junctate

Myocyte Enhancer Factor 2 Activates Promoter Sequences of the Human AβH-J-J Locus, Encoding Aspartyl-β-Hydroxylase, Junctin, and Junctate

E-Box Sites and a Proximal Regulatory Region of the Muscle Creatine Kinase Gene Differentially Regulate Expression in Diverse Skeletal Muscles and Cardiac Muscle of Transgenic Mice

Human SRF-related proteins: DNA-binding properties and potential regulatory targets.

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