A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus.

Donoghue, Maria J.; Ernst, Heidemarie; Wentworth, Bruce M.; Nadal‐Ginard, Bernardo; Rosenthal, Nadia

doi:10.1101/gad.2.12b.1779

Cited by 212 publications

(133 citation statements)

References 46 publications

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“…Though a number of muscle promoters have been characterized, this element is the smallest sequence identified to contain sufficient information for muscle-specific expression. Other cis-acting regions that have been shown to confer muscle-specific expression in heterologous promoter constructs include the creatine kinase (M) gene enhancer (257 to 352 bp) (23,45), the myosin light chain 1/3 gene enhancer (0.9 kilobase-pair) (10), and a 67-bp segment of the cardiac troponin T promoter (27). The troponin gene segment contains a sequence motif that is present in other muscle genes but appears to be different from the skeletal actin MRE.…”

Section: Srementioning

confidence: 99%

Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes.

Walsh¹

1989

Mol. Cell. Biol.

112

121

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A conserved 28-base-pair element in the skeletal actin promoter was sufficient to activate muscle-specific expression when placed upstream of a TATA element. This muscle regulatory element (MRE) is similar in structure to the serum response element (SRE), which is present in the promoters of the c-fos proto-oncogene and the nonmuscle actin genes. The SRE can function as a constitutive promoter element. Though the MRE and SRE differed in their tissue-specific expression properties, both elements bound to the same protein factors in vitro. These proteins are the serum response factor (SRF) and the muscle actin promoter factors 1 and 2 (MAPF1 and MAPF2). The SRF and MAPF proteins were resolved by chromatographic procedures, and they differed in their relative affinities for each element. The factors were further distinguished by their distinct, but overlapping, methylation interference footprint patterns on each element. These data indicate that the differences in tissue-specific expression may be due to a complex interaction of protein factors with these sequences.

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Section: Srementioning

confidence: 99%

Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes.

Walsh¹

1989

Mol. Cell. Biol.

112

121

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“…The sequence of the mutated 156-bp fragment was confirmed by dideoxy sequence analysis. The reference plasmid pMSVpgal contains the bacterial lacZ gene under the control of the murine sarcoma virus long terminal repeat (14). The control expression plasmid pMT2 and the eukaryotic expression plasmid pMT2-GATA-4 were described previously (4).…”

mentioning

confidence: 99%

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

Ip¹,

Wilson²,

Heikinheimo³

et al. 1994

Mol. Cell. Biol.

171

104

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The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineagerestricted zinc finger transcription factor GATA-4. This (7, 10,27,35,48,65,81). Therefore, an understanding of muscle cell development must at some level be based upon elucidating the molecular mechanisms that control lineage-specific gene expression during myogenesis.The recent identification and characterization of the basic helix-loop-helix myogenic transcription factors, including MyoD, myogenin, Myf-5, and MRF-4/herculin/Myf-6, as well as the MEF-2 family of transcription factors has added significantly to our understanding of skeletal myogenesis (8, 9,12,15,18,40,41,43,58,59,76,80). These factors bind to and regulate the expression of many skeletal muscle-specific genes (47,48,64,70). In contrast, relatively little is currently understood about the molecular mechanisms that control cardiac muscle-specific gene expression during mammalian development. Despite the fact that overlapping sets of genes are expressed in the heart and skeletal muscle, several lines of evidence suggest that distinct transcriptional programs may regulate these processes. For example, basic helix-loop-helix myogenic transcription factors are not expressed in developing heart or precardiac mesoderm (49,63,64), and mice contain-* Corresponding author. Mailing address:

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“…(iii) Although a significant portion of the rat MLC1/3 locus analyzed to date has been shown to have no detectable role in the regulation of MLC transcription during terminal differentiation of myogenic cells in vitro (2), it remains possible that additional cis-acting elements are required for activation of the MLC locus in the developmental pathway from mesodermal stem cell to committed myoblast in vivo. To address these questions we generated several lines of transgenic mice carrying multiple copies of a reporter gene linked to the MLC -enhancer.…”

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confidence: 99%

“…In the rat, transcriptional activation of the myosin light chain (MLC)1/3 locus in skeletal muscle occurs -4 days before birth, when transcripts originating at the MLC1 promoter encode the predominant alkali light chain isoform (1). A recent analysis of this locus (2) suggests that activation of rat MLC transcription in tissue culture is not regulated by sequences associated with either the MLC1 or the MLC3 promoter, which alone are insufficient to induce expression of linked CAT or thymidine kinase reporter genes in established muscle cell lines. In addition, 15 kilobases (kb) of intragenic and upstream extragenic sequences from the MLC1/3 locus have been tested by enhancer trap assays in tissue culture and do not contain any cis-acting regulatory elements.…”

mentioning

confidence: 99%

Myosin light chain enhancer activates muscle-specific, developmentally regulated gene expression in transgenic mice.

Rosenthal

Kornhauser

Donoghue

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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106

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The rat myosin light chain (MLC)1/3 gene locus contains a potent muscle-specific enhancer, located downstream of the coding region, greater than 24 kilobases away from the MLC1 transcription start site. To assess the role of this enhancer in the activation of MLC expression during development, transgenic mice were generated carrying multiple copies of a MLC1 promoter-chloramphenicol acetyltransferase (CAT) transcription unit linked to a genomic fragment including the enhancer. CAT expression was detected in four mouse lines, up to 1000-fold higher in skeletal muscles than in other tissues. Activation of endogenous MLC1 transcription in these animals 4 days before birth was reflected in the onset of CAT transgene expression. This study identifies the transcriptional control elements necessary to activate the 21-kilobase MLC1/3 locus at the appropriate fetal stage and indicates that the MLC enhancer is sufficient to induce developmentally regulated expression from the MLC1 promoter exclusively in skeletal muscle cells.

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A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus.

Cited by 212 publications

References 46 publications

Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes.

Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes.

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

Myosin light chain enhancer activates muscle-specific, developmentally regulated gene expression in transgenic mice.

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