ArticleThe Journal of biological chemistry2013
Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
80 citing papers in PubMed, 136 citations in OpenAlex.
- Modified relative dose response values differ between lactating women in the United States and Indonesia.Experimental biology and medicine (Maywood, N.J.) · 2020Trial
- Provitamin A-biofortified maize consumption increases serum xanthophylls andExperimental biology and medicine (Maywood, N.J.) · 2017Trial
- High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.The American journal of clinical nutrition · 2015Trial
- Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.The American journal of clinical nutrition · 2014Trial
- Inactivity of human β,β-carotene-9',10'-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Genetic ancestry and genotype-by-diet interactions shape plasma carotenoid metabolism in humans.Research square · 2026Article
- Dietary Carotenoid Intake and Sleep: A Narrative Review of Evidence from Human and In Vivo Animal Studies.Nutrients · 2026Review
- ChEA-KG and ChEA-KG-TS: a network-based transcription factor enrichment analysis tool with an accompanying time-series workflow.Nucleic acids research · 2026Article
- An Integrated Single-Cell Atlas of the Mouse Ileum Links Nutrient Metabolism with Epithelial and Immune Crosstalk.The Journal of nutrition · 2025Article
- Decoding Hypercarotenemia: Integrating Pathophysiology, Clinical Recognition, and Precision Management.Cureus · 2025Review
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Rescue of the Stargardt Disease Phenotype inFASEB bioAdvances · 2025Article
- Recent advances in carotenoid absorption, distribution, and elimination.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Loss of the vitamin A receptor RBPR2 in mice disrupts whole-body retinoid homeostasis and the quantitative balance regulating retinylidene protein synthesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Distinct pathways for the absorption and metabolism of β-carotene and zeaxanthin in the mouse intestine.Journal of lipid research · 2025Article
- Vitamin A supply in the eye and establishment of the visual cycle.Current topics in developmental biology · 2025Review
- Immunometabolic effects ofImmunometabolism (Cobham, Surrey) · 2024Review
- The Absorption, Storage, and Transport of Ocular Carotenoids and Retinoids.Annual review of vision science · 2024Review
- Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.American journal of physiology. Endocrinology and metabolism · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Low dietary intake of β-carotene is associated with chronic disease and vitamin A deficiency. β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-15,15'-monoxygenase (BCMO1) to support vision, reproduction, immune function, and cell differentiation. Considerable variability for this key step in vitamin A metabolism, as reported in the human population, could be related to genetics and individual vitamin A status, but it is unclear how these factors influence β-carotene metabolism and vitamin A homeostasis. Here we show that the intestine-specific transcription factor ISX binds to the Bcmo1 promoter. Moreover, upon induction by the β-carotene derivative retinoic acid, this ISX binding decreased expression of a luciferase reporter gene in human colonic CaCo-2 cells indicating that ISX acts as a transcriptional repressor of BCMO1 expression. Mice deficient for this transcription factor displayed increased intestinal BCMO1 expression and produced significantly higher amounts of vitamin A from supplemental β-carotene. The ISX binding site in the human BCMO1 promoter contains a common single nucleotide polymorphism that is associated with decreased conversion rates and increased fasting blood levels of β-carotene. Thus, our study establishes ISX as a critical regulator of vitamin A production and provides a mechanistic explanation for how both genetics and diet can affect this process.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.