ArticlePLoS genetics2007
An unmethylated 3' promoter-proximal region is required for efficient transcription initiation.
Article in PLoS genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
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- Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations.Nature communications · 2021Article
- An Analysis of Methylome Evolution in Primates.Molecular biology and evolution · 2021Article
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- Cytosine methylations in the promoter regions of genes involved in the cellular oxidation equilibrium pathways affect rice heat tolerance.BMC genomics · 2020Article
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- Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma.Clinical epigenetics · 2017Article
- Decrease of 5hmC in gastric cancers is associated with TET1 silencing due to with DNA methylation and bivalent histone marks at TET1 CpG island 3'-shore.Oncotarget · 2015Article
- A DNA methylation signature associated with the epigenetic repression of glycine N-methyltransferase in human hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2013Article
- Discovering high-resolution patterns of differential DNA methylation that correlate with gene expression changes.Nucleic acids research · 2013Article
- Epigenetic programming and risk: the birthplace of cardiovascular disease?Stem cell reviews and reports · 2013Review
- Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation.Developmental cell · 2013Article
- DNA methylation and differentiation: silencing, upregulation and modulation of gene expression.Epigenomics · 2013Review
- Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research.British journal of cancer · 2012Review
- Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.Molecular cell · 2011Article
- Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Epigenetic Silencing of ALDH1L1, a Metabolic Regulator of Cellular Proliferation, in Cancers.Genes & cancer · 2011Article
- A concise review on epigenetic regulation: insight into molecular mechanisms.International journal of molecular sciences · 2011Review
- Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The promoter regions of approximately 40% of genes in the human genome are embedded in CpG islands, CpG-rich regions that frequently extend on the order of one kb 3' of the transcription start site (TSS) region. CpGs 3' of the TSS of actively transcribed CpG island promoters typically remain methylation-free, indicating that maintaining promoter-proximal CpGs in an unmethylated state may be important for efficient transcription. Here we utilize recombinase-mediated cassette exchange to introduce a Moloney Murine Leukemia Virus (MoMuLV)-based reporter, in vitro methylated 1 kb downstream of the TSS, into a defined genomic site. In a subset of clones, methylation spreads to within approximately 320 bp of the TSS, yielding a dramatic decrease in transcript level, even though the promoter/TSS region remains unmethylated. Chromatin immunoprecipitation analyses reveal that such promoter-proximal methylation results in loss of RNA polymerase II and TATA-box-binding protein (TBP) binding in the promoter region, suggesting that repression occurs at the level of transcription initiation. While DNA methylation-dependent trimethylation of H3 lysine (K)9 is confined to the intragenic methylated region, the promoter and downstream regions are hypo-acetylated on H3K9/K14. Furthermore, DNase I hypersensitivity and methylase-based single promoter analysis (M-SPA) experiments reveal that a nucleosome is positioned over the unmethylated TATA-box in these clones, indicating that dense DNA methylation downstream of the promoter region is sufficient to alter the chromatin structure of an unmethylated promoter. Based on these observations, we propose that a DNA methylation-free region extending several hundred bases downstream of the TSS may be a prerequisite for efficient transcription initiation. This model provides a biochemical explanation for the typical positioning of TSSs well upstream of the 3' end of the CpG islands in which they are embedded.
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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.