Figure 5.

ZBED6 controls DOCK3 transcription in sepsis‐induced muscle atrophy. A) Integrated analysis of RNA‐seq data from nine depots of skeletal muscles of septic WT and ZBED6‐deficient pigs and ZBED6 ChIP‐seq data from pig muscle tissue reveals four potential targets for ZBED6. B) Expression fold change values (Log₂ of TPM) of SOX18, DOCK3, C14orf39, and G0S2 in the RNA‐seq analysis from nine depots of muscles of septic WT and ZBED6‐deficient pigs. Triceps brachii; TB, Biceps brachii; BB, Rectus abdominis; RA, Longissimus dorsi muscle; LD, Psoas major muscle; PMM, Gastrocnemius; GAS, Tibialis anterior; TA, Extensor digitorum lateralis; EDL, Soleus; SOL. C) Plot (significance vs fold change) of significantly putative ZBED6 target genes (|fold change |≥ 2 and ‐Log₁₀P value ≥ 2) between WT and ZBED6‐deficient pigs. D) DOCK3 mRNA expression in the 9 depots of skeletal muscles of septic WT and ZBED6‐deficient pigs. E) DOCK3 protein expression in the EDL muscle of septic WT and ZBED6‐deficient pigs. F) The wildtype and ZBS mutant sequences are indicated. Cell‐based reporter assays were performed in pig primary satellite cells of ZBED6‐deficient and WT pigs transfected with the wildtype or ZBS mutant luciferase reporter. G) Luciferase analysis showing the effects of ZBED6 on wild‐type DOCK3‐ZBS luciferase (ZBS‐LUC) or mutant DOCK3‐ZBS luciferase (mZBS‐LUC). Data were calculated from three independent replicates. H) ChIP analysis of ZBED6 on DCOK3‐ZBS promoter region was performed in gastrocnemius muscle. Data were calculated from three independent replicates. Data are expressed as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001.