Fig. 6: MLL4 and MEF2 function cooperatively to control Nt5c1a and Ampd3 expression.

a, b MLL4-dependent regulation of Nt5c1a and Ampd3 gene expression. (Top) ChIP-seq binding profiles for MLL4 in WT and Mll4SET MKO muscle. mRNA-seq data from WT and Mll4SET MKO muscle is shown at the bottom, indicating a high correlation of the two datasets. Input, genomic DNA from myocytes. c Expression of genes (qRT–PCR) involved in AMP metabolism in GC muscles from the indicated genotypes. Ampd3, WT, n = 5; MKO, n = 5 mice per group. Nt5c1a, Nt5c2, Ak1, Adk, Ada, WT, n = 6; MKO, n = 6 mice per group. P value: <0.0001, 0.0067. d MLL4 and MEF2D ChIP-seq tracks from myocytes at the Ampd3 and N5c1a loci. Data obtained from published datasets GSE138994 and GSE43223 were analyzed. e Putative conserved MEF2-binding site within the intron 1 of mouse Ampd3 gene. f AAV-mediated overexpression of MEF2C in WT and Mll4SET MKO muscle. Ex1, exon 1. g (Left) Representative Western blot analysis of protein extracts prepared from GC muscles of indicated mice subjected to AAV-mediated overexpression of MEF2C. (Right) Quantification of the AMPD3/GAPDH signal ratios were normalized (=1.0) to WT GFP controls. n = 5 mice per group. *P value: <0.0001. ^#P value: <0.0001. All data are shown as the mean ± SEM. **P < 0.01, ***P < 0.001 vs. corresponding WT controls, ^###P < 0.001 versus corresponding GFP controls, determined by two-tailed unpaired Student’s t-test (c) or one-way ANOVA (g) coupled to Fisher’s least significant difference (LSD) post-hoc test. Source data are provided as a Source data file.