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. 2004 Oct 1;18(19):2348–2353. doi: 10.1101/gad.1234304

Figure 1.

Figure 1.

The p38 pathway and Mef2D are rate-limiting for late-stage genes. (A) Examples of simple network motifs based on Lee et al. (2002). In a single-input motif, factor A directly regulates the three targets B, C, and D. The simple cascade depicts sequential activation with only gene B directly activated by A. In the feed-forward loop, A directly regulates each gene and sequential activation is achieved by requiring both A and B to express gene C, and both A and C to express gene D. (B) MDER fibroblasts were induced to differentiate for varying times and analyzed by Northern and Western blot. (SB) Treatment of cells with SB203580; (CIP) phosphatase treatment prior to SDS-PAGE. (C) Ratio of the average gene expression in each temporal cluster of MyoD-activated genes comparing cells constitutively expressing MKK6E or treated with SB203580 with the expression in untreated cells, demonstrating effects of p38 activity on clusters of genes activated at different stages of differentiation. Ratios are in log2 space; a value of 0 indicates no treatment change, a value of 1 indicates a twofold increase due to the treatment, and a value of -1 indicates a twofold reduction. Microarray expression data was generated from MDER cells induced to differentiate for 24 h with MKK6E-expressing virus or control virus, and analyzed together with previously generated data for control and SB203580-treated MDER cells (Bergstrom et al. 2002). Clusters 1-6 are the earliest to latest activated clusters, and cluster 7 is a transiently expressed group of genes (Bergstrom et al. 2002). Error bars represent standard error, except cluster 7, where error bars are absent because only one gene from this cluster was affected. ANOVA p-value < 0.0001 for both MKK6E and SB203580. Post-hoc testing indicated that cluster 6 differs significantly from the other clusters in response to MKK6E. (D) MDER cells were infected with the indicated retroviruses, induced to differentiate for 12 h, and subjected to Northern analysis for late-stage genes Myh3 and Des and the early-stage gene Cdh15. Mef2 is the Mef2D isoform, Con is an empty control retrovirus.