Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element.

Shen, Rong-Fong; Goswami, Shyamal; Mascareno, Eduardo; Kumar, Ashok; Siddiqui, M.A.Q.

doi:10.1128/mcb.11.3.1676

Cited by 48 publications

(39 citation statements)

References 79 publications

(83 reference statements)

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“…Ventricular MLC2 gene was the experimental marker of choice for elucidation of tissue-specific regulation of gene activity, as it exhibits strict cardiac tissue specificity (2,50,54). Although previous studies have characterized cardiogenesis by immunochemical and/or molecular approaches (6,14,17,23,37,49,58,59), little information is available on molecular events in early stages of development during which the committed precardiac mesoderm enters cardiogenic differentiation.…”

Section: Resultsmentioning

confidence: 99%

Differential expression of the myocyte enhancer factor 2 family of transcription factors in development: the cardiac factor BBF-1 is an early marker for cardiogenesis.

Goswami¹,

Qasba²,

Ghatpande³

et al. 1994

Mol. Cell. Biol.

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In the present study, we have used single chicken blastoderms of defined early developmental stages, beginning with the prestreak stage, stage 1 (V. Hamburger and H. L. Hamilton, J. Morphol. 88:49-92, 1951), to analyze the onset of cardiac myogenesis by monitoring the appearance of selected cardiac muscle tissue-specific gene transcripts and the functional expression of the myocyte enhancer factor 2 (MEF-2) proteins. Using gene-specific oligonucleotide primers in reverse transcriptase PCR assay, we have demonstrated that the cardiac myosin light-chain 2 (MLC2) and alpha-actin gene transcripts appear as early as stage 5, i.e., immediately after the cardiogenic fate assignment at stage 4. Consistent with this observation is the developmental expression pattern of DNA-binding activity of BBF-1, a cardiac muscle-specific member of the MEF-2 protein family, which also begins at stage 5 prior to MEF-2. Differential expression of DNA-binding complexes is also observed with another AT-rich DNA sequence (CArG box) as probe, but the binding pattern with the ubiquitous TATA-binding proteins remains unchanged during the same developmental period. Thus, the cardiogenic commitment and differentiation of the precardiac mesoderm, as exemplified by the appearance of cardiac MEF-2, MLC2, and alpha-actin gene products, occur earlier than previously thought and appear to be closely linked. The onset of skeletal myogenic program follows that of the cardiogenic program with the appearance of skeletal MLC2 at stage 8. We also observed that mRNA for the MEF-2 family of proteins appears as early as stage 2 and that for CMD-1, the chicken counterpart of MyoD, appears at stage 5. The temporal separation of activation of cardiac and skeletal MLC2 genes, which appears immediately after the respective fate assignments, and those of cardiac MEF-2 and CMD-1, which occur before, are consistent with the established appearance of the myogenic programs and with the acquisition pattern of the two tissue-specific morphological characteristics in the early embryo. The preferential appearance of BBF-1 activity in precardiac moesderm, relative to that of MEF-2, indicates that these two protein factors are distinct members of the MEF-2 family and provides a compelling argument in support of the potential role of BBF-1 as a regulator of the cardiogenic cell lineage determination, while cardiac MEF-2 might be involved in maintenance of the cardiac differentiative state.

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Section: Resultsmentioning

confidence: 99%

Differential expression of the myocyte enhancer factor 2 family of transcription factors in development: the cardiac factor BBF-1 is an early marker for cardiogenesis.

Goswami¹,

Qasba²,

Ghatpande³

et al. 1994

Mol. Cell. Biol.

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“…The main characteristic of active repression is that it can turn off the expression of a gene efficiently irrespective of the nature and number of the activator proteins present in the cell (40). The active mode of repression has been shown to be especially important in cell type-specific regulation of genes, such as neural-specific type II sodium channel and SCG10 gene (41) and erythroid-specific expression of the 15-lipoxygenase and avian cardiac MLC-2 gene (42,43). Our data show that ERP is capable of inhibiting expression from the minimum ␣-MHC gene promoter and acts independently of the position of the PNR element in the gene.…”

Section: Discussionmentioning

confidence: 99%

Single-stranded DNA-binding Proteins PURα and PURβ Bind to a Purine-rich Negative Regulatory Element of the α-Myosin Heavy Chain Gene and Control Transcriptional and Translational Regulation of the Gene Expression

Gupta

Sueblinvong

Raman

et al. 2003

Journal of Biological Chemistry

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The ␣-myosin heavy chain is a principal molecule of the thick filament of the sarcomere, expressed primarily in cardiac myocytes. The mechanism for its cardiacrestricted expression is not yet fully understood. We previously identified a purine-rich negative regulatory (PNR) element in the first intron of the gene, which is essential for its cardiac-specific expression (Gupta, M., Zak, R., Libermann, T. A., and Gupta, M. P.

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“…It is possible that other negativeacting elements are also involved in silencing and cooperate with synapsin I NRSE to induce repression in nonneuronal cells. Alternatively, as in the case of most silencer elements identified so far (23)(24)(25)(26)(27)(28)(29)(30)(31), synapsin I NRSE may work with neuron-specific positive-acting elements to achieve neuronspecific expression of the synapsin I gene. The observation that the pSyI-233 MU construct is still capable of directing preferential expression of a fusion gene in neuronal cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of a functional silencer element involved in neuron-specific expression of the synapsin I gene.

Suzuki

Mori

et al. 1993

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

153

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We have identified a functional silencer element (positions -231 to -211) in the human synapsin I gene that selectively represses its transcription in nonneuronal cells. Transfection experiments using synapsin I4uciferase constructs show that site-specific mutations or deletion of this silencer sequence results in expression of the reporter gene in nonneuronal cells. Moreover, the silencer element is caabl of conferring repression on a heterologous promoter in nonneuronal cells. Gel-shift assays reveal the presence of a sequencespecific synapsin I silencer-binding protein in nonneuronal cel extracts but not in neuronal cell extracts. Mutagenesis studies of the silencer sequence demonstrate that formation of the specific silencer-protein complex in vitro correlates well with repression of transcription in Wivo. These data indicate that the interaction between synapsin I silencer and its binding protein is involved in tissue-specific expression of the synapsin I gene.In addition, our results suggest the existence of at least one additional cis-acting element within the promoter-proximal region (positions -233 to +20) that also contributes to the neuron-specific expression of the synapsin I gene.Synapsin I, a peripheral membrane protein of small synaptic vesicles, is present at presynaptic nerve terminals throughout both the central and peripheral nervous systems. The interactions of synapsin I with synaptic vesicles and cytoskeletal elements and the regulation of these interactions by phosphorylation have been implicated in modulation of neurotransmitter release (1, 2). Synapsin I includes two isoforms, Ia and Ib, that are alternatively spliced products from a single gene (3). During development, expression of synapsin I correlates temporally with synaptogenesis (4,5).The synapsin I gene was recently cloned (6). Study of its 5' flanking sequences revealed several positive and negative regulatory regions (7-9). However, the cis-acting elements and trans-acting factors for directing the tissue-specific and developmental stage-specific expression ofsynapsin I have not been identified. The 1460The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element.

Cited by 48 publications

References 79 publications

Differential expression of the myocyte enhancer factor 2 family of transcription factors in development: the cardiac factor BBF-1 is an early marker for cardiogenesis.

Differential expression of the myocyte enhancer factor 2 family of transcription factors in development: the cardiac factor BBF-1 is an early marker for cardiogenesis.

Single-stranded DNA-binding Proteins PURα and PURβ Bind to a Purine-rich Negative Regulatory Element of the α-Myosin Heavy Chain Gene and Control Transcriptional and Translational Regulation of the Gene Expression

Identification of a functional silencer element involved in neuron-specific expression of the synapsin I gene.

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