ArticleNature2015
Competition between DNA methylation and transcription factors determines binding of NRF1.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 296 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
296 citing papers in PubMed, 526 citations in OpenAlex.
- Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3-year survival update and multi-omics analysis.Clinical and translational medicine · 2025Trial
- Gene regulatory mechanisms downstream of DNA methylation.Nature reviews. Genetics · 2026Review
- Cumulative transcription factor binding and p300-mediated histone acetylation drive enhancer activation frequency.Nature genetics · 2026Article
- DNA hypomethylation enables the transcriptional repressor SlSPL-CNR to control fruit flavor ester biosynthesis.Nature communications · 2026Article
- Folic acid deficiency in cancer therapy: a review of chemotherapy-induced malabsorption and supportive care strategies.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation.The EMBO journal · 2026Article
- Article
- An inducible system to study the regulatory functions of GSX2 in human lateral ganglionic eminence-like progenitors.Developmental biology · 2026Article
- Promoter hypomethylation drives ABCB1-mediated carfilzomib resistance in multiple myeloma.Clinical epigenetics · 2026Article
- Distinctive DNA sequence features define epigenetic longevity of inflammatory memory.Science (New York, N.Y.) · 2026Article
- Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice.Cell death and differentiation · 2026Article
- Mechanisms of gene regulation by SRCAP and H2A.Z.Nature communications · 2026Article
- Challenges and advances in drug resistance and tolerance in cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.Genome biology · 2026Article
- Many roads lead to a plant cistrome: mapping and interpreting transcription factor binding in plants.Genome biology · 2026Review
- Genetics and environment distinctively shape the human immune cell epigenome.Nature genetics · 2026Article
- Allelic Variation in Maize Malate Dehydrogenase 7 Shapes Promoter Methylation and Banded Leaf and Sheath Blight Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy.Blood · 2025Article
- Coordinated epigenetic dysregulation of CNR1 and FAAH genes drives endocannabinoid system dysfunction in anorexia nervosa.Journal of eating disorders · 2025Article
236 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic transcription factors (TFs) are key determinants of gene activity, yet they bind only a fraction of their corresponding DNA sequence motifs in any given cell type. Chromatin has the potential to restrict accessibility of binding sites; however, in which context chromatin states are instructive for TF binding remains mainly unknown. To explore the contribution of DNA methylation to constrained TF binding, we mapped DNase-I-hypersensitive sites in murine stem cells in the presence and absence of DNA methylation. Methylation-restricted sites are enriched for TF motifs containing CpGs, especially for those of NRF1. In fact, the TF NRF1 occupies several thousand additional sites in the unmethylated genome, resulting in increased transcription. Restoring de novo methyltransferase activity initiates remethylation at these sites and outcompetes NRF1 binding. This suggests that binding of DNA-methylation-sensitive TFs relies on additional determinants to induce local hypomethylation. In support of this model, removal of neighbouring motifs in cis or of a TF in trans causes local hypermethylation and subsequent loss of NRF1 binding. This competition between DNA methylation and TFs in vivo reveals a case of cooperativity between TFs that acts indirectly via DNA methylation. Methylation removal by methylation-insensitive factors enables occupancy of methylation-sensitive factors, a principle that rationalizes hypomethylation of regulatory regions.
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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.