Fig. 2: Obesity-associated increase in MAFG signaling links nutrient states to lncRNA repression.
From: A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism
a Illustration of transcription factor-binding site (TFBS) analysis and a list of TFBS enriched in promoters of mRNAs (blue) or lncRNAs (orange) affected by HFD vs. CD feeding (n = 3 each). TFBS is from UniProbe (U) or Jaspar (J). b qPCR of smMAF (Maff, Mafg, and Mafk) expression in C57BL/6N and Dock7m mice (n = 4 each). c Published BLRP ChIP-seq in livers of mice transduced with adenovirus (Ad)-overexpressing BLRP-MAFG fusion proteins (GEO ID: GSE77559)40 was used as a proxy for MAFG cistromes in the liver. BLRP-MAFG peaks per gene were determined in a ±50-kb window around the TSS (defined as ±1 bp from gene start) of expressed, induced, or repressed lncRNAs by HFD using window function in bedtools75. d qPCR of L-DIO-lncRNAs and Mafg mRNA in livers of Ad-MAFG vs. Ad-CMV mice (n = 5 each). e qPCR of lncRNA exhibiting MAFG binding within TSS ± 50 kb, as identified by BLRP-MAFG ChIP-Seq and Mafg expression after transfection of primary hepatocytes with 100 nM Mafg or Scr LNAs, n = 4–5 experiments, each performed in triplicates. f UCSC Genome Browser with expression of selected lncRNAs (“RNA-Seq”) and BLRP-MAFG binding (“ChIP-Seq” from Vallim et al.40) in the liver. g Motif activity of smMAF and MAFA TFBS across nutritional states and HFD feeding analyzed using ISMARA41 (n = 3–4 per group). h Venn diagram illustrating DGE overlap and enriched gene ontology (GO) categories shared between indicated nutritional states, diets, and genotypes. i Log2R Cf of mRNA (blue) and lncRNA (orange) expression changes in livers of Ad-MAFG vs. Ad-CMV mice (n = 4 each). d, e Bar graphs represent mean ± s.e.m. with all data points plotted, and statistical differences were calculated using d unpaired or e paired, two-tailed Student’s t test. h Significance of gene overlaps was calculated by using a hypergeometric distribution: *p < 0.05, **p < 0.01, ***p < 0.001. Source data are provided as a Source Data file. Illustration in (a) was created with BioRender.com.
