ArticleMolecular and cellular biology2000
Genomic targeting of methylated DNA: influence of methylation on transcription, replication, chromatin structure, and histone acetylation.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- Genomic context sensitizes regulatory elements to genetic disruption.Molecular cell · 2024Article
- Genomic context sensitizes regulatory elements to genetic disruption.bioRxiv : the preprint server for biology · 2024Article
- Overcoming the Silencing of Doxycycline-Inducible Promoters in hiPSC-derived Cardiomyocytes.Open research Europe · 2024Article
- Expression and localization of HPG axis-related genes in Carassius auratus with different ploidy.Frontiers in endocrinology · 2024Article
- Decrease ofFrontiers in medicine · 2022Article
- Targeted transcript analysis in muscles from patients with genetically diverse congenital myopathies.Brain communications · 2022Article
- TRIM27 Functions as a Novel Oncogene in Non-Triple-Negative Breast Cancer by Blocking Cellular Senescence through p21 Ubiquitination.Molecular therapy. Nucleic acids · 2020Article
- Epigenetic modification and therapeutic targets of diabetes mellitus.Bioscience reports · 2020Review
- Article
- Hepatocyte Nuclear Factor 4-Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver.Hepatology (Baltimore, Md.) · 2019Article
- Epigenetics andFrontiers in genetics · 2019Review
- Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation.Nucleic acids research · 2017Article
- Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia.Genomics · 2017Article
- Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.Nature genetics · 2017Article
- DICER1 regulates endometrial carcinoma invasion via histone acetylation and methylation.Journal of Cancer · 2017Article
- A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands.Nucleic acids research · 2016Article
- Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms.Gene · 2016 · on this mapReview
- Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms.Beilstein journal of nanotechnology · 2016Review
- Competition between DNA methylation and transcription factors determines binding of NRF1.Nature · 2015Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
We have developed a strategy to introduce in vitro-methylated DNA into defined chromosomal locations. Using this system, we examined the effects of methylation on transcription, chromatin structure, histone acetylation, and replication timing by targeting methylated and unmethylated constructs to marked genomic sites. At two sites, which support stable expression from an unmethylated enhancer-reporter construct, introduction of an in vitro-methylated but otherwise identical construct results in specific changes in transgene conformation and activity, including loss of the promoter DNase I-hypersensitive site, localized hypoacetylation of histones H3 and H4 within the reporter gene, and a block to transcriptional initiation. Insertion of methylated constructs does not alter the early replication timing of the loci and does not result in de novo methylation of flanking genomic sequences. Methylation at the promoter and gene is stable over time, as is the repression of transcription. Surprisingly, sequences within the enhancer are demethylated, the hypersensitive site forms, and the enhancer is hyperacetylated. Nevertheless, the enhancer is unable to activate the methylated and hypoacetylated reporter. Our findings suggest that CpG methylation represses transcription by interfering with RNA polymerase initiation via a mechanism that involves localized histone deacetylation. This repression is dominant over a remodeled enhancer but neither results in nor requires region-wide changes in DNA replication or chromatin structure.
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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.