Fold Change (Group 2 vs. Group 1) Grp 1 Grp 2 ABC DE Supplemental Figure 1. Metabolomic comparison of control groups. Analysis (PCA) illustrating the unsupervised.

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Fold Change (Group 2 vs. Group 1) Grp 1 Grp 2 ABC DE Supplemental Figure 1. Metabolomic comparison of control groups. Analysis (PCA) illustrating the unsupervised relationship between A. Control Group 1 (Brg1 floxed/floxed ;aMHC-Cre-ERT +/0 ;Brm -/- minus tamoxifen treatment) and Control Group 2 (Brg1 floxed/floxed ;aMHC-Cre-ERT 0/0 (no transgene);Brm -/- mice plus tamoxifen treatment). B. Partial Least Squares Discriminant Analysis (PLS-DA) score visualizes supervised (assigned group) clustering of Control Group 1 and Control Group 2. C. PLS-DA score plots for Control Group 1 heart metabolites (red) compared to metabolites identified in Control Group 2 hearts (green). Each point represents the combined metabolite profile in an individual mouse. Variable Importance in Projection (VIP) plot of VIP statistical analysis identifying the top 15 metabolites. D. T-test significant metabolites between Control Group 1 and Control Group 2. E. Unsupervised heat maps of all identified metabolites and their associated fold changes in Control Group 1 vs. Control Group 2. N=3 (Control Group 1), N=3 (Control Group 2) hearts per group analyzed. Each point represents an individual mouse heart run in parallel with the other samples.

Alanine Increased ~1.3 fold Threonine Increased ~1.4 fold Serine Increased >2 fold Glycine Pyruvate  -Ketoglutarate Glutamate Acetyl-CoA Alanine amino- transferase Serine dehydratase Serine Hydroxymethyl transferase Serine Hydroxymethyl transferase Pyruvate Dehydrogenase Cysteine X 2 Reactions Tryptophan X 4 Reactions Supplemental Figure 2. Metabolic pathways related to cardiac Brg1/Brm double-mutant activity based on t-test significant metabolites (Figure 2D) not otherwise identified by pathway analysis (Table 2). A. Alanine metabolism, B. Creatine and creatinine metabolism. Figures adapted from: and Wyss and Kaddurah-Daouk (2000 Creatine and creatinine metabolism. Physiol Rev 80, ). A. Alanine metabolism B. Creatine and creatinine metabolism ADPATP H2OH2OPiPi Creatinine Decreased to ~0.6 fold Creatine Phosphoryl- Creatine Phosphoryl- Creatinine H2OH2O PiPi H2OH2O S-Adenosyl-L-Homocysteine S-Adenosyl-L-Methionine SAM-GAMT (N-guanidinoacetate methyltransferase) Guanidino- Acetate L-Arginine L-Ornithine H2OH2O Urea Glycine

Supplemental Figure 3. RT-qPCR analysis of Pfk1-fb1 mRNA levels normalized to Gapdh levels in hearts from Brg1/Brm double-mutant mice compared to controls. Each histogram shows the relative expression (mean + SE for two independent experiments). Pfk1 mRNA Levels /GAPDH (Relative Units) Control Group 2Brg1/Brm DM (Group 3)