ArticleNature genetics2022
Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and repeat repression by DNA methylation.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- DNA methylation of genes involved in lipid metabolism drives adiponectin levels and metabolic disease.Diabetologia · 2026Pooled it
- Exercise and nutrition as epigenetic regulators of gene expression: an exploratory scoping review with bibliometric analysis.Frontiers in nutrition · 2026Pooled it
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Whole-genome DNA methylation analysis reveals distinct subtype characteristics in epithelial ovarian cancer.Cancer gene therapy · 2026Article
- Exploring the Role of DNA Methylation in the Epigenetic Landscape of Cancer.Biochemical genetics · 2026Review
- Gene regulatory mechanisms downstream of DNA methylation.Nature reviews. Genetics · 2026Review
- HIV immunological nonresponders show low SKAP1 concentration and DNA hypermethylation in the SKAP1 promotor region.AIDS (London, England) · 2026Article
- Dynamic neuro-immune regulation of psychiatric risk loci in human neurons.Nature communications · 2026Article
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- Enhancing the performance and interpretability of epigenetic clocks.Nucleic acids research · 2026Article
- DNA hypomethylation enables the transcriptional repressor SlSPL-CNR to control fruit flavor ester biosynthesis.Nature communications · 2026Article
- Investigating PeripheralBiomolecules · 2026Article
- TiSMeD: A tissue-specific methylation and expression database for biomarker and translational applications.Molecular therapy. Nucleic acids · 2026Article
- Epigenetic lockdown of type I interferon sensing and signalling in human pluripotent cells.Nature communications · 2026Article
- Review
- Continuous DNA methylation deconvolution-based surrogate for B-cell differentiation state in chronic lymphocytic leukemia.Communications medicine · 2026Article
- Deep learning-driven prediction of on-target activity, off-target risk, and repair outcomes in CRISPR/Cas9: current landscape and multi-scale perspectives.Journal of translational medicine · 2026Review
- Inferring gene-regulatory networks using epigenomic priors.iScience · 2026Article
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosine methylation efficiently silences CpG-rich regulatory regions of genes and repeats in mammalian genomes. To what extent this entails direct inhibition of transcription factor (TF) binding versus indirect inhibition via recruitment of methyl-CpG-binding domain (MBD) proteins is unclear. Here we show that combinatorial genetic deletions of all four proteins with functional MBDs in mouse embryonic stem cells, derived neurons or a human cell line do not reactivate genes or repeats with methylated promoters. These do, however, become activated by methylation-restricted TFs if DNA methylation is removed. We identify several causal TFs in neurons, including ONECUT1, which is methylation sensitive only at a motif variant. Rampantly upregulated retrotransposons in methylation-free neurons feature a CRE motif, which activates them in the absence of DNA methylation via methylation-sensitive binding of CREB1. Our study reveals methylation-sensitive TFs in vivo and argues that direct inhibition, rather than indirect repression by the tested MBD proteins, is the prevailing mechanism of methylation-mediated repression at regulatory regions and repeats.
Indexed as
Identifiers
What Socratic 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 Socratic graph.