Figure 5.

YY1 regulates dystrophin and DAPC expression and is negatively correlated to human fiber diameter. (a) Bubble plots showing the distribution and size of negatively correlated overrepresented GO pathways between the Gcn5^skm−/− differentially expressed gene set and a Yy1-KO study gene set (Gene Expression Omnibus accession no. GSE39009). TPR, tetratricopeptide repeat. (b) Relative expression of genes in differentiated primary mouse myotubes from four individual empty vector control (Con) or Yy1-overexpressing (Yy1 OE) lentivirus-transduced colonies for Gcn5, Pcaf, DAPC, cell surface, and ECM protein–expressing genes (Dmd, Utrn, Sgcb, Sgcd, Sntb1, Actn1, Actn2, Lama2, Lamc1, Lamc2, Itga4) and muscle-specific genes Ttn and Ckm as determined by RT-qPCR. n = 4 (from four independent colonies selected after lentiviral transduction). *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus Gcn5^skm+/+ as measured by two-tailed Student’s t test. (c) Western blot of dystrophin protein from empty vector control (Con) and YY1-overexpressing (YY1 OE) mouse primary myotubes and stain-free protein loading control. Data are presented as mean ± SEM for controls and Gcn5^skm−/− mice. n = 3/group. *, P < 0.05 versus Gcn5^skm+/+ as measured by two-tailed Student’s t test. (d) Scatterplots showing correlations of either GCN5 or YY1 transcripts (Z-score of TMM-normalized TPM) with three representative structural muscle transcripts (DMD, UTRN, and SGCD) in human skeletal muscle transcriptome (Gene Expression Omnibus accession no. GSE111017; n = 119). (e) Correlation between mean minimum Feret diameter of human muscle fibers, consisting of 250 measured muscle fibers from 192 GTEx samples (GTExPortal database version 8) and YY1 (Log2 TPM) transcript expression. Representative images of GTEx muscle samples are shown. Scale bars, 200 μm.