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Vitamin B2 Sensing by the Nuclear Receptor AhR Reprograms Hepatic Metabolism [ChIP-Seq]

GSE341320 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing 54 samples Submitted 2026/08/01 Platform GPL30173Platform GPL34284Platform GPL34290
Summary
Nuclear receptors such as RAR/RXR and VDR directly sense vitamins A and D, but analogous sensing mechanisms for most other vitamins remain unknown. Here we identify a metabolite sensing pathway linking vitamin B2 (riboflavin) availability to an adaptive gene expression program. Riboflavin deficiency limits the FAD-dependent enzyme kynurenine 3-monooxygenase, leading to accumulation of kynurenine, an endogenous ligand of the aryl hydrocarbon receptor (AhR). Kynurenine-induced AhR nuclear translocation selectively activates poised hepatic enhancers in cooperation with AP-1 and C/EBPα, inducing glucuronidation genes and the FAD synthase gene FLAD1. This response is required to maintain intracellular FAD levels and support cell fitness under riboflavin-limiting conditions. In vivo, dietary riboflavin deficiency enhances hepatic drug clearance and reduces irinotecan toxicity. Together, these findings reveal a vitamin-sensing mechanism in which a cofactor-dependent enzyme acts as the sensor and AhR functions as the transcriptional effector that enables both flavin homeostasis and hepatic clearance capacity.
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Direct links to NCBI, no account and no request form: the whole study as GSE341320_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 54 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1501350 and SRA study SRP721051. Searching any of these in the dataset finder brings you back here.

Study design
15 conditions, mostly in duplicate
HepG2_Day12_Cont_H3K27ac_ChIP ×5 HepG2_Day12_B2_minus_H3K27ac_ChIP ×5 AhR_flox_Hepatocyte_Cont_Ad_Cont_H3K27ac_ChIP ×3 AhR_flox_Hepatocyte_B2_minus_Ad_Cont_H3K27ac_… ×3 AhR_flox_Hepatocyte_Cont_Ad_Cre_H3K27ac_ChIP ×3 HepG2_Cont_DMSO_Day12_H3K27ac_ChIP ×2 HepG2_B2_minus_DMSO_Day12_H3K27ac_ChIP ×2 HepG2_B2_minus_AhRinh_Day12_H3K27ac_ChIP ×2 +8 more

Supports a between-group comparison across 39 samples.

15 replicated groups read from the first 40 of 54 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.

Samples in this study

+ 14 more — browse all 54 samples with per-sample file links →

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