ArticleNature genetics2019
MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation.
Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.The British journal of dermatology · 2020Pooled it
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Review
- Cell Cycle Control of Nuclear Metabolism Couples Phosphatidylinositol Signaling to Histone Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Native chromatome profiling reveals hundreds of metabolic enzymes in the nucleus across tissues.Nature communications · 2026Article
- A KLF5's domino effect drives metastatic pancreatic cancer.Molecular cancer · 2026Article
- CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1.Molecular cancer · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis.Science (New York, N.Y.) · 2025Article
- Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions.Nature communications · 2025Article
- Regulation of gene expression through protein-metabolite interactions.npj metabolic health and disease · 2025Review
- MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.Redox report : communications in free radical research · 2024Article
- Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity.Nature communications · 2024Article
- Nuclear localization of MTHFD2 is required for correct mitosis progression.Nature communications · 2024Article
- Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.Science advances · 2024Article
- The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.Molecular oncology · 2024Article
- Detection of differential bait proteoforms through immunoprecipitation-mass spectrometry data analysis.Scientific data · 2024Article
- MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions.npj metabolic health and disease · 2024Review
- MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.Cell death & disease · 2024Article
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
37 authors at 7 institutions in 4 countries.
Funding
Abstract
The histone acetyl reader bromodomain-containing protein 4 (BRD4) is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1 (methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1). We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression; pharmacological inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin associated suggests a direct role for nuclear metabolism in the control of gene expression.
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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.