Fast-Muscle-Specific Expression of Human Aldolase A Transgenes

Salminen, Marjo; Maire, Pascal; Concordet, Jean Paul; Moch, Clara; Porteu, Arlette; Kahn, Axel; Daegelen, Dominique

doi:10.1128/mcb.14.10.6797-6808.1994

Cited by 4 publications

(1 citation statement)

References 61 publications

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“…In this regard, it is interesting to note that overexpression of NFI in CEFs produces the same epithelioid, highly adherent phenotype as is observed when these cells are transformed by v-ski (41,42). NFI has also been implicated in muscle-specific transcriptional regulation (43)(44)(45) and again there is a highly suggestive correlation with the activity of ski. In mice NFI regulation of aldolase transgenes is limited to fast-twitch fibers (45); the same fiber type affected by overexpression of ski in transgenic mice (28).…”

Section: Discussionmentioning

confidence: 74%

DNA Binding and Transcriptional Activation by the Ski Oncoprotein Mediated by Interaction with NFI

Tarapore

Richmond²,

Zheng

et al. 1997

Nucleic Acids Research

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The Ski oncoprotein has been found to bind non-specifically to DNA in association with unindentified nuclear factors. In addition, Ski has been shown to activate transcription of muscle-specific and viral promoters/enhancers. The present study was undertaken to identify Ski's DNA binding and transcriptional activation partners by identifying specific DNA binding sites. We used nuclear extracts from a v-Ski-transduced mouse L-cell line and selected Ski-bound sequences from a pool of degenerate oligonucleotides with anti-Ski monoclonal antibodies. Two sequences were identified by this technique. The first (TGGC/ANNNNNT/GCCAA) is the previously identified binding site of the nuclear factor I (NFI) family of transcription factors. The second (TCCCNNGGGA) is the binding site of Olf-1/EBF. By electophoretic mobility shift assays we find that Ski is a component of one or more NFI complexes but we fail to detect Ski in Olf-1/EBF complexes. We show that Ski binds NFI proteins and activates transcription of NFI reporters, but only in the presence of NFI. We also find that homodimerization of Ski is essential for co-activation with NFI. However, the C-terminal dimerization domain of c-Ski, which is missing in v-Ski, can be substituted by the leucine zipper domain of GCN4.

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Section: Discussionmentioning

confidence: 74%

DNA Binding and Transcriptional Activation by the Ski Oncoprotein Mediated by Interaction with NFI

Tarapore

Richmond²,

Zheng

et al. 1997

Nucleic Acids Research

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Expression of myogenin during embryogenesis is controlled by Six/ sine oculis homeoproteins through a conserved MEF3 binding site

Spitz

Demignon

Porteu

et al. 1998

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

209

201

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Myogenin, one of the MyoD family of proteins, is expressed early during somitogenesis and is required for myoblast fusion in vivo. Previous studies in transgenic mice have shown that a 184-bp myogenin promoter fragment is sufficient to correctly drive expression of a ␤-galactosidase transgene during embryogenesis. We show here that mutation of one of the DNA motifs present in this region, the MEF3 motif, abolished correct expression of this ␤-galactosidase transgene. We have found that the proteins that bind to the MEF3 site are homeoproteins of the Six͞sine oculis family. Antibodies directed specifically against Six1 or Six4 proteins reveal that each of these proteins is present in the embryo when myogenin is activated and constitutes a muscle-specific MEF3-binding activity in adult muscle nuclear extracts. Both of these proteins accumulate in the nucleus of C2C12 myogenic cells, and transient transfection experiments confirm that Six1 and Six4 are able to transactivate a reporter gene containing MEF3 sites. Altogether these results establish Six homeoproteins as a family of transcription factors controlling muscle formation through activation of one of its key regulators, myogenin.

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Genomic sequences of aldolase C (Zebrin II) direct lacZ expression exclusively in non-neuronal cells of transgenic mice

Walther

Dichgans

Maricich

et al. 1998

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

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Aldolase C is regarded as the brain-specific form of fructose-1,6-bisphosphate aldolase whereas aldolase A is regarded as muscle-specific. In situ hybridization of mouse central nervous system using isozyme-specific probes revealed that aldolase A and C are expressed in complementary cell types. With the exception of cerebellar Purkinje cells, aldolase A mRNA is found in neurons; aldolase C message is detected in astrocytes, some cells of the pia mater, and Purkinje cells. We isolated aldolase C genomic clones that span the entire protein coding region from 1.5 kb 5 to the transcription start site to 0.5 kb 3 to the end of the last exon. The bacterial gene, lacZ, was inserted in two different locations and the constructs tested in transgenic mice. When the protein coding sequences were replaced with lacZ, three of five transgenic lines expressed ␤-galactosidase only in cells of the pia mater; one line also expressed in astrocyte-like cells. When lacZ was inserted into the final exon (and all structural gene sequences were retained) transgene expression was observed in astrocytes in all regions of the central nervous system as well as in pial cells. Thus, with the exception of Purkinje cell expression, the behavior of the full-length transgene mimics the endogenous aldolase C gene. The results with the shorter transgene suggest that additional enhancer elements exist within the intragenic sequences. The absence of Purkinje cell staining suggests that the cis elements required for this expression must be located outside of the sequences used in this study.

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Fast-Muscle-Specific Expression of Human Aldolase A Transgenes

Cited by 4 publications

References 61 publications

DNA Binding and Transcriptional Activation by the Ski Oncoprotein Mediated by Interaction with NFI

DNA Binding and Transcriptional Activation by the Ski Oncoprotein Mediated by Interaction with NFI

Expression of myogenin during embryogenesis is controlled by Six/ sine oculis homeoproteins through a conserved MEF3 binding site

Genomic sequences of aldolase C (Zebrin II) direct lacZ expression exclusively in non-neuronal cells of transgenic mice

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