Fig. 6.

DUX4 induces signatures of a stem-cell-like and less-differentiated state. (A) Transcripts that were upregulated (red) by DUX4 and tMALDUX4VP16 (tDUX4VP16) but downregulated (green) by tMALDUX4ERD (tDUX4ERD) were considered as positively correlated (upregulated) with DUX4 activity. Conversely, transcripts that were downregulated (green) by DUX4 and tMALDUX4VP16 but upregulated (red) by tMALDUX4ERD were considered as negatively correlated (downregulated) with DUX4 activity. Transcripts upregulated (red) by tMALDUX4 and DUX4c were considered as positively correlated (upregulated) with DUX4c activity. Conversely, transcripts downregulated (green) by tMALDUX4 and DUX4c were considered as negatively correlated (downregulated) with DUX4c activity. (B–D) We constructed a single-sample DUX4 expression score from our study in mouse to examine overlap with DUX4 target genes identified by other studies. (B,C) Our mouse DUX4 expression score distinguishes murine C2C12 myoblasts expressing DUX4 from controls in two independent published microarray studies (Bosnakovski et al., 2008b; Sharma et al., 2013). (D) Our mouse DUX4 expression score also distinguishes DUX4-expressing human immortalised myoblasts from those expressing DUX4-s or eGFP control (Geng et al., 2012). (E) A human DUX4 signature derived from human myoblasts expressing DUX4 (Geng et al., 2012) distinguishes mouse myoblasts expressing tMALDUX4 and DUX4c both from those expressing DUX4 or tMALDUX4–VP16, and also from those expressing tMALDUX4–ERD. (F) Signalling entropy is elevated in the transcriptional profiles induced by DUX4 and tMALDUX4–VP16 but is reduced by tMALDUX4–ERD expression, supporting the hypothesis that DUX4 inhibits myogenic differentiation. Boxes represent the interquartile range (central 50% of data) with the median indicated by a line, and whiskers indicate the extremes of the distribution. P-values were calculated using Student's t-test. RV, retrovirus.