ArticleProceedings of the National Academy of Sciences of the United States of America2019
Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Telomere-to-telomere genome ofHorticulture research · 2026Article
- DNA methylation, nucleic acid structure, and rett mutations tune MeCP2 binding affinity and cooperativity.The Journal of biological chemistry · 2026Article
- A modeller's guide for biomedical discovery.Disease models & mechanisms · 2026Article
- MeCP2 requires interactions with nucleosome linker DNA to read chromatin DNA methylation.Nature communications · 2026Article
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- MeCP2 interacts with the super elongation complex to regulate transcription.Science advances · 2025Article
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- Probabilistic and machine-learning methods for predicting local rates of transcription elongation from nascent RNA sequencing data.Nucleic acids research · 2025Article
- Article
- Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons.Nature microbiology · 2024Article
- MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation.Nature communications · 2024Article
- The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- DNA-sequence and epigenomic determinants of local rates of transcription elongation.bioRxiv : the preprint server for biology · 2023Article
- Stochastic modeling of the mRNA life process: A generalized master equation.Biophysical journal · 2023Article
- Bayesian inference of polymerase dynamics over the exclusion process.Royal Society open science · 2023Article
- Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets.Genome research · 2023Article
- Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models.Nature communications · 2023Article
- Epigenetic and epitranscriptomic regulation of axon regeneration.Molecular psychiatry · 2023Review
- A screen for MeCP2-TBL1 interaction inhibitors using a luminescence-based assay.Scientific reports · 2023Article
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates "slow sites" in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shockwaves in nonequilibrium physics transport models. This mechanism differs from conventional gene-regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings point to a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene-expression patterns are choreographed.
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