Fig. 5
Effect of TCDD on nicotinamide biosynthesis. (A) Nicotinamide biosynthesis pathway. (B–D) Urinary tryptophan, trigonelline, and 1-methylnicotinamide levels as measured by 1-D 1H NMR (n = 5). Data was normalized by creatinine and subsequently probabilistic quotient normalization. An asterisk (*) indicates significance from a post hoc Dunnett test (p ≤ 0.05). Mean and standard deviation are shown. (E) Heatmap of dose dependent effects of TCDD on gene expression associated with nicotinamide biosynthesis. pDREs were determined by a position weight matrix with a Matrix Similarity Score (MSS) cut off of ≥ 0.856 based on the sequence of characterized functional DREs. ChIP-seq analysis detected AHR genomic binding in mouse liver 2 h after oral gavage with 30 μg/kg TCDD (GSE97634). The green tiles indicate an FDR of ≤ 0.05. In the dose response bulk RNA-seq gene expression, the black flags indicate a P1(t) ≥ 0.8. The Counts column refers to the maximum estimate of aligned reads of each gene where a lower level of expression (≤ 500 reads) is depicted in yellow and a higher level of expression (≥ 10,000) is depicted in pink. ACMS Aminocarboxymuconate semialdehyde, AMS Aminomuconate semialdehyde, NAMN Nicotinic acid mononucleotide, NA Nicotinic acid, NAAD Nicotinic acid dinucleotide, NAD Nicotinamide dinucleotide, NMN Nicotinamide mononucleotide, 2PY N-methyl-2-pyridone-5-carboxamide, 4PY N-methyl-4-pyridone-3-carboxamide.
