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...e functional significance of bivalent domains, we examined gene expression patterns across the three cell types with at least ten bivalent domains (ES cells, C2C12, and Neuro2a) (Mogass et al., 2004; =-=Tomczak et al., 2004-=-; Perez-Iratxeta et al., 2005). Within each cell type, we found that genes marked by Lys4 methylation tend to be expressed at significantly higher levels than those associated with Lys27 methylation (...

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...ttp://www.ncbi.nlm.nih.gov/ projects/geo). Data for myogenesis were obtained from published studies using the in vitro model of C2C12 myoblasts undergoing differentiation induced by serum restriction =-=(24,25)-=-. Adipocyte differentiation in vitro was induced by hormonal treatment on two distinct models: the 3T3L1 preadipocyte cell line (26), and NIH-3T3 fibroblasts (27). Two distinct cell models were also u...

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...cell proliferation, differentiation, and fusion (Mendias et al. 2004) and is expressed in rapidly proliferating C2C12 cells grown in high serum but subsequently down-regulated during differentiation (=-=Tomczak et al. 2004-=-). Additionally, id2, gli3, and notch1 are highly expressed in the R + cell population and are rapidly up-regulated in C2C12 cells after withdrawal of serum, indicating that these genes are expressed ...

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...ic et al. (54), as provided by the authors, were input directly into ProteinCenter. To compare the gene expression data, the list of detected genes as provided by Moran et al. (55) and Tomczak et al. =-=(56)-=- were converted to International Protein Index or Swiss-Prot protein accession numbers using either the Protein Identifier CrossReference Service (57) or IDconverter (58), and these protein accession ...

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...e of bivalent domains, we examined gene expressionspatterns across the three cell types with at least 10 bivalent domains (ES cells, C2C12, Neuro2a)s(Mogass et al., 2004; Perez-Iratxeta et al., 2005; =-=Tomczak et al., 2004-=-). Within each cell type, wesfound that genes marked by H3K4me3 tend to be expressed at significantly higher levels than thosesassociated with H3K27me3 (Figure 4). A good example is the Ebf1 gene, whi...

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...ast differentiation, such as mitogens and Notch signaling, we do not yet have a good understanding of the events that occur in vivo to overcome these inhibitory signals and to induce differentiation at a specific time and place. A feed-forward circuit as a quantal step How does a single transcription factor execute an entire program of cell differentiation? How does a single event result in a predictable and complex response? Microarray expression studies of cultured C2C12 cells have shown that expression levels of many RNAs change during skeletal muscle differentiation (Delgado et al., 2003; Tomczak et al., 2004). To determine how many of these changes are caused by the expression and activity of Myod, we assessed gene expression changes in fibroblasts with an inducible Myod protein and observed a similarly large number of expression changes with ~5% of the genes tiled on the array (Bergstrom et al., 2002). Many of the RNAs that showed increased expression in response to Myod were muscle-specific genes, such as skeletal muscle myosins and actins, but many were genes expressed in numerous different lineages, such as the Mef2 transcription factors. Surprisingly, some RNAs induced by Myod coded for prote...

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...genetic study and the tight linkage of the Ltbp4 allele to dye uptake support a model whereby there is a close interplay between membrane leak and surrounding fibrosis. Ltbp4 is highly expressed in muscle and therefore positioned to be a determinant of damage and fibrosis in muscle diseases (14, 15). It is also notable that there was a functional correlate of these pathological features in that the D2-Sgcg mice had muscle weakness. The expression of LTBP4 in muscle is not restricted to fibroblasts, since Ltbp4 mRNA levels are increased in the C2C12 cell culture model of muscle differentiation (29). Therefore, multiple cell types in skeletal muscle mediate the deposition of LTBP4 into the matrix and sequestration of TGF-β (Figure 8). We found that insertion of 12 amino acids into the proline-rich region of LTBP4 resulted in reduced susceptibility to proteolysis associated with reduced SMAD signaling. These data are consistent with recent results generated from fibroblasts deficient for LTBP4 (16). Fibroblasts deficient for LTBP4 are impaired in their ability to activate TGF-β, consistent with a requirement of LTBP4 for normal TGF-β activation. In LTBP4-deficient fibroblasts, reexpressio...

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...rformed extensive analysis of muscle-derived gene expression profiles (9–11). This included the analysis of muscle differentiation using a well-established model, the mouse myoblast cell line (C2C12) =-=(12)-=-. Two primary transcription factors regulating this process are MyoD and Myogenin, but many other regulatory elements have been identified [reviewed in (13) and (14)]. For a better understanding of ho...

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... transcripts to be significantly differentially expressed between myoblasts and myotubes. Gene ontology annotations overrepresented for these transcripts were in good agreement with published results =-=[22]-=- (Table S4). In comparison to the amount of differentially expressed transcripts, a much higher number of TSSs (3,498) were associated with modification changes between myoblasts and myotubes. Althoug...