Fig. 4: MOF-mediated transcription signature in adipose tissue.

a Schematic representation of strategy used for bulk mRNA-seq analysis of visceral WAT of Mof^+/+ and Mof^+/− mice fed SD or HFD. Analysis (i) queries the differentially regulated genes (DEGs) between genotypes (DEG_geno) to determine effect of Mof depletion. Analysis (ii) queries DEGs between diets (DEG_diet) independently for each genotype to determine effect of HFD. b Heatmap showing Z-score expression of DEG_geno for SD and HFD treatments. DEG_geno of SD and HFD were combined (n = 4,088) and unbiasedly grouped into five clusters based on expression similarity. A number of genes per cluster (right), genotypes (top; Mof^+/+: black and Mof^+/−: dark green), and diets (top; SD: gray and HFD: light green) are indicated. Network map (bottom) showing the significant enriched pathways for cluster 1 genes. Circles indicate the number of genes within each pathway. Color scale represents p adjust values. See Supplementary Fig. 5a–d and Supplementary Data 3. False discovery rates (FDR) were controlled by the Benjamini–Hochberg method having q value defined as 0.05. c Heatmaps showing the H3-normalized ChIP enrichment on MOF-bound peaks sorted by enrichment intensity and clusters based on unbiased clustering (k-means = 2). Enrichment signal is plotted relative to MOF-peak center ±3 kb. Color scale represents the Log₂ fold change. See also: Supplementary Fig. 5e and Supplementary Data 4. d Circos plot showing MOF ChIP-seq and mRNA-seq data integration. Significantly downregulated (p < 0.05) genes in Mof^+/− are shown in gray, MOF-bound genes present in cluster 1 (#1, blue) or 2 (#2, yellow) are depicted. The inner lines show the common downregulated and bound genes in #1 (dark blue) or #2 (dark yellow). The lower panel displays the significantly enriched KEGG pathways associated with common genes. The scale shows the −Log(q value). Pathways directly related to adipocyte energy metabolism are highlighted in bold. False discovery rates (FDR) were controlled by the Benjamini–Hochberg method having q value defined as 0.05. e Significantly enriched pathways associated with changes in diet of Mof^+/+ and Mof^+/− mice (DEG_Diet). Segments in the heatmap are separated (top to bottom) according to common deregulated pathways, pathways enriched only in Mof^+/+ and pathways enriched only in Mof^+/−. Scale shows −Log(q value). Pathways related to the development of obesity are highlighted in bold. See also: Supplementary Fig. 5.