ArticleHuman molecular genetics2011
DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
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- Roles of transposable elements and DNA methylation in the formation of CpG islands and CpG-depleted regulatory elements.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes.Genome research · 2025Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
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- Analysis of regulatory sequences in exosomal DNA of NANOGP8.PloS one · 2023Article
- Role of primary aging hallmarks in Alzheimer´s disease.Theranostics · 2023Review
- Regulation of arsenic methylation: identification of the transcriptional region of the human AS3MT gene.Cell biology and toxicology · 2022Article
- DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival.Breast cancer research : BCR · 2022Article
- Harnessing the Full Potential of Multi-Omic Analyses to Advance the Study and Treatment of Chronic Kidney Disease.Frontiers in nephrology · 2022Review
- The SulfotransferaseInternational journal of environmental research and public health · 2021Article
- Virtual Gene Concept and a Corresponding Pragmatic Research Program in Genetical Data Science.Entropy (Basel, Switzerland) · 2021Review
- Epigenetic Dysregulation ofCancers · 2021Article
- DNA Methylation and Immune Memory Response.Cells · 2021Review
- Single-molecule micromanipulation studies of methylated DNA.Biophysical journal · 2021Article
- Identification of ZBTB18 as a novel colorectal tumor suppressor gene through genome-wide promoter hypermethylation analysis.Clinical epigenetics · 2021Article
48 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
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Abstract
Despite the fact that 45% of all human gene promoters do not contain CpG islands, the role of DNA methylation in control of non-CpG island promoters is controversial and its relevance in normal and pathological processes is poorly understood. Among the few studies which investigate the correlation between DNA methylation and expression of genes with non-CpG island promoters, the majority do not support the view that DNA methylation directly leads to transcription silencing of these genes. Our reporter assays and gene reactivation by 5-aza-2'-deoxycytidine, a DNA demethylating agent, show that DNA methylation occurring at CpG poor LAMB3 promoter and RUNX3 promoter 1(RUNX3 P1) can directly lead to transcriptional silencing in cells competent to express these genes in vitro. Using Nucleosome Occupancy Methylome- Sequencing, NOMe-Seq, a single-molecule, high-resolution nucleosome positioning assay, we demonstrate that active, but not inactive, non-CpG island promoters display a nucleosome-depleted region (NDR) immediately upstream of the transcription start site (TSS). Furthermore, using NOMe-Seq and clonal analysis, we show that in RUNX3 expressing 623 melanoma cells, RUNX3 P1 has two distinct chromatin configurations: one is unmethylated with an NDR upstream of the TSS; another is methylated and nucleosome occupied, indicating that RUNX3 P1 is monoallelically methylated. Together, these results demonstrate that the epigenetic signatures comprising DNA methylation, histone marks and nucleosome occupancy of non-CpG island promoters are almost identical to CpG island promoters, suggesting that aberrant methylation patterns of non-CpG island promoters may also contribute to tumorigenesis and should therefore be included in analyses of cancer epigenetics.
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