ArticleCell reports2025
Temporally discordant chromatin accessibility and DNA demethylation define short- and long-term enhancer regulation during cell fate specification.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed.
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- Time-course ATAC-seq and RNA-seq analysis of porcine synovium-derived mesenchymal stem cells under in vitro osteogenic induction.Epigenetics & chromatin · 2026Article
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- DNA methylation profiles aid to identify putative genome activation histories along lymphomagenesis.NAR genomics and bioinformatics · 2026Article
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- 5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer.Communications medicine · 2026Article
- 5mC and 5hmC methylation sequencing: the power of 6-base sequencing in a multiomic era.Epigenomics · 2026Review
- Mechanisms and therapeutic prospects of DNA methylation-mucosal innate immunity crosstalk in inflammatory bowel disease.Frontiers in immunology · 2026Review
- Physicochemical features of intrinsically disordered regions predict DNA-demethylation-promoting activity of transcription factors.Epigenetics & chromatin · 2025Article
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Article
- The paradigm shift in neural stem cells basic research driven by artificial intelligence related technologies.Frontiers in cellular neuroscience · 2025Review
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Abstract
Chromatin and DNA modifications mediate the transcriptional activity of lineage-specifying enhancers, but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly resolved timeline of their dynamics during neural progenitor cell differentiation. We discovered that, while complete demethylation appears delayed relative to shorter-lived chromatin changes for thousands of enhancers, DNA demethylation actually initiates with 5-hydroxymethylation before appreciable accessibility and transcription factor occupancy is observed. The extended timeline of DNA demethylation creates temporal discordance appearing as heterogeneity in enhancer regulatory states. Few regions ever gain methylation, and resulting enhancer hypomethylation persists long after chromatin activities have dissipated. We demonstrate that the temporal methylation status of CpGs (mC/hmC/C) predicts past, present, and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to shape short- and long-term enhancer regulation during cell fate specification.
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