Fig. 4: CR reprograms beta-cell gene regulatory networks (GRNs).

A SCENIC heatmap with hierarchical clustering analysis of TF activity in beta cells from AL, CR and HFD mice after 2 months on diet. TFs identified as āONā are shown in black, while TFs identified as āOFFā are in white. B Pearson correlation matrix of nā=ā272 TF identified in all mouse beta cells (all diet groups together). Boxes highlight clusters of TFs with a high degree of correlation. C Gene regulatory networks (GRNs) formed by TFs identified using SCENIC in beta cells from AL, CR and HFD mice. TFs are shown as pink nodes, while target protein-coding genes are shown in blue. Node size represents the ābetweenness centralityā measurements that report the influence of a given TF within a network. D Dot plot and hierarchical clustering showing the gene expression levels of target genes associated with Atf6 and Mafa GRNs from AL, CR, and HFD beta cells. The dot plot scale shows the relative expression level and percentage of cells expressing a target gene.