ArticleNature metabolism2021
Cell-surface SLC nucleoside transporters and purine levels modulate BRD4-dependent chromatin states.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Impact of Trastuzumab and Pertuzumab on HER2 Localization and the Estrogen Receptor Cistrome in ER+/HER2+ Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- USP5 regulates purine metabolism and represents a therapeutic target in esophageal cancer.Cell death & disease · 2026Article
- Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Lipid Transport Pathways: A New Frontier in Colorectal Cancer Therapy.Digestive diseases and sciences · 2025Review
- MEBOCOST maps metabolite-mediated intercellular communications using single-cell RNA-seq.Nucleic acids research · 2025Article
- Specialized molecular pathways drive the formation of light-scattering assemblies in leucophores.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Membrane transporters modulating the toxicity of arsenic, cadmium, and mercury in human cells.Life science alliance · 2025Article
- KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.Nature communications · 2025Article
- Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024Article
- Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer.EMBO molecular medicine · 2023Article
- Membrane transporters in cell physiology, cancer metabolism and drug response.Disease models & mechanisms · 2023Review
- Cancer metabolites: promising biomarkers for cancer liquid biopsy.Biomarker research · 2023Review
- To metabolomics and beyond: a technological portfolio to investigate cancer metabolism.Signal transduction and targeted therapy · 2023Review
- Metabolic Fuel for Epigenetic: Nuclear Production Meets Local Consumption.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 2 countries.
Funding
Abstract
Metabolism negotiates cell-endogenous requirements of energy, nutrients and building blocks with the immediate environment to enable various processes, including growth and differentiation. While there is an increasing number of examples of crosstalk between metabolism and chromatin, few involve uptake of exogenous metabolites. Solute carriers (SLCs) represent the largest group of transporters in the human genome and are responsible for the transport of a wide variety of substrates, including nutrients and metabolites. We aimed to investigate the possible involvement of SLC-mediated solutes uptake and cellular metabolism in regulating cellular epigenetic states. Here, we perform a CRISPR-Cas9 transporter-focused genetic screen and a metabolic compound library screen for the regulation of BRD4-dependent chromatin states in human myeloid leukaemia cells. Intersection of the two orthogonal approaches reveal that loss of transporters involved with purine transport or inhibition of de novo purine synthesis lead to dysfunction of BRD4-dependent transcriptional regulation. Through mechanistic characterization of the metabolic circuitry, we elucidate the convergence of SLC-mediated purine uptake and de novo purine synthesis on BRD4-chromatin occupancy. Moreover, adenine-related metabolite supplementation effectively restores BRD4 functionality on purine impairment. Our study highlights the specific role of purine/adenine metabolism in modulating BRD4-dependent epigenetic states.
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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.