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. 2019 Dec 19;4(24):e132402. doi: 10.1172/jci.insight.132402

Figure 2. Epigenomic programs in steroid-treated dystrophic mouse muscles.

Figure 2

(A) PCA of H3K27ac profiles derived from quadriceps myofibers. Weekly vs. daily prednisone regimens cluster from each other and from vehicle-treated controls. (B) Motif enrichment analysis highlights GRE, KRE, and MEF2 as acetylation-enriched motifs after weekly prednisone, while FOXO3 motifs were enriched after daily prednisone. (C) Concordant genes enriched for both H3K27ac and expression included Klf15 and Mef2C after weekly prednisone, while daily prednisone promoted acetylation and expression of Foxo3 and other atrophy genes. (D) Representative H3K27ac markings across gene loci of interest demonstrated divergent acetylation enrichment with respect to weekly or daily prednisone (signal is tags/bp normalized to 1e7 reads; red arrows, gain; blue arrow, loss of H3K27ac signal). (E) Pathway analysis showed that pulsatile weekly prednisone increased transcription of genes regulating glucose, fatty acid, and BCAA metabolism. H3K27ac ChIP-seq showed GR enrichment after both weekly and daily steroids, but it showed increased enrichment of KRE and MEF2 sites only after weekly prednisone. ChIP-qPCR confirmed enriched occupancy for GR, KLF15, and MEF2C on the same sites (n = 3 mice/group for K27ac ChIP-seq, n = 5 mice/group for RNA-seq; q value, Benjamini-Hochberg test).