Disease relevance of Vgll2

• Here we describe that VITO-1, a new SID (scalloped interaction domain)-containing protein, binds to TEF1 in vitro and strongly stimulates transcription of a MCAT reporter plasmid together with TEF-1 [1].

Psychiatry related information on Vgll2

• Likewise, expression of human Vito-1 during fetal and adult human development was found exclusively in skeletal muscle preferentially in fast skeletal muscles [2].

High impact information on Vgll2

• In skeletal muscle, TEF-1 factors interact with a skeletal muscle-specific cofactor called Vestigial-like 2 (Vgl-2) that is related to the Drosophila protein Vestigial [3].
• Vgl-1 and Vgl-3 transcripts are enriched in the placenta, whereas Vgl-2 is expressed in the differentiating somites and branchial arches during embryogenesis and is skeletal muscle-specific in the adult [4].
• Together these observations suggest that the activation of the Epo gene in the large majority of these F-MuLV-induced erythroleukemic cell lines establishes an autocrine loop resulting in the constitutive activation of the Epo receptor signal transduction pathway, thereby conferring a growth and survival advantage in vito and in vitro [5].
• However, the mechanism whereby Vgl-2 regulates TEF-1 factors and the requirement for Vgl-2 for muscle-specific gene expression were not known [6].
• These results demonstrate that Vgl-2 is required for muscle gene expression, in part by switching DNA binding of TEF-1 factors during muscle differentiation [6].

Biological context of Vgll2

• In addition, interference with VITO-1 expression by siRNA attenuated differentiation of C2C12 muscle cells and MyoD-dependent myogenesis in 10T1/2 cells [1].

Anatomical context of Vgll2

• Since VITO-1 is predominantly expressed in the skeletal muscle lineage, it might serve as an essential transcriptional intermediary factor to promote muscle-specific expression via MCAT cis-regulatory elements [1].
• By Northern blot analysis, we found VITO-1 to be up-regulated in C2C12 myotubes although some expression can be detected in proliferating C2C12 myoblasts [2].
• Using an antisense morpholino, we blocked the expression of Vgl-2 and a muscle-specific gene in the myogenic C2C12 cell line and in chick embryos by electroporation [6].
• In situ hybridization revealed co-expression of Vgl-2 with myogenin in the differentiating muscle of embryonic myotomes but not in newly formed somites prior to muscle differentiation [4].
• In vito experiments further showed that retro-inversion of a T-cell epitope causes its inability to either sustain in vitro T-cell stimulation or to prime specific T cells [7].

Physical interactions of Vgll2

• Here, gel mobility shift assays show that Vgl-2 differentially affects DNA binding of different TEF-1 factors [6].

Other interactions of Vgll2

• Instead, TEF-1 factors rely on the muscle-specific cofactor Vestigial-like 2 (Vgl-2), a protein related to Drosophila vestigial [6].

Analytical, diagnostic and therapeutic context of Vgll2

• Using whole-mount hybridzation and Northern blot analysis, we showed that VITO-1 is expressed in the somitic myotome from E8.75 mouse embryos onwards and later on in skeletal muscle but not in the heart [2].

References