Fig. 5: Inhibition of SUMOylation improves PPARγ transcriptional activity and its synergy with PGC-1α.
From: IRX3 controls a SUMOylation-dependent differentiation switch in adipocyte precursor cells
To investigate how hyperactivated SUMOylation suppresses adipogenesis in IRX3-KO cells, the effect of SUMOylation inhibition on PPARγ activity was assessed. a Differential expression of Pparg and downstream target genes in IRX3-KO vs. control ME3 cells on day 1 of differentiation (n \(=\) 6); data from14. Experimentally validated binding of upstream transcription factors to the promoters of each adipogenic regulator in WT adipogenic cells is shown to the right; ChIP-seq data collected from the UCSC Genome Browser hub UniBind 2021143. Transcription factors experimentally shown to be SUMOylated in WT preadipocytes or mature adipocytes are marked with (S), data from50. b Luciferase activity of a reporter gene under control of 3 × PPRE sites, co-transfected with PPARγ and/or PGC-1α in ME3 cells. Firefly luciferase units relative to the control group and normalized to constitutive Renilla luciferase is shown; n \(=\) 3 replicates from one out of two independent experiments. **padj \(=\) 0.001, ***padj < 0.001, overexpression of PGC-1α and/or PPARγ compared to empty plasmid; #padj < 0.05, ##padj < 0.01, ###padj < 0.001, comparison between DMSO, rosi and/or ML-792, two-way ANOVA with Holm-Sidak correction for multiple testing. The data were square-root-transformed prior to statistical analyses. The bar graphs show means \(\pm \,\)SD. Source data are provided in the Source Data file.
