ArticleScientific reports2021
Transcriptional overlap links DNA hypomethylation with DNA hypermethylation at adjacent promoters in cancer.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 36 citations in OpenAlex.
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Epigenetic paradigm of DNA methylation for understanding the pathophysiology, diagnostics, and therapeutics in sarcomas.Epigenomics · 2025Review
- Beyond Structure: Methylation Fine-Tunes Stability and Folding Kinetics of bcl2Mid G-Quadruplex.Angewandte Chemie (International ed. in English) · 2025Article
- Review
- Apoptotic effect of melatonin on ER-positive breast cancer cell lines: ADGRL4 gene expression and promoter methylation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- DNA Hypomethylation Underlies Epigenetic Swapping betweenEpigenomes · 2024Article
- Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response.European journal of medical research · 2023Article
- Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma.Functional & integrative genomics · 2023Article
- Identification of Cancer/Testis Antigens Related to Gastric Cancer Prognosis Based on Co-Expression Network and Integrated Transcriptome Analyses.Advanced biomedical research · 2023Article
- Twist1 Promoter Methylation Regulates the Proliferation and Apoptosis of Acute Myeloid Leukemia Cells via PI3K/AKT Pathway.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Identification of Tissue-Specific Gene Clusters Induced by DNA Demethylation in Lung Adenocarcinoma: More Than Germline Genes.Cancers · 2022Article
- Immunotherapy response and microenvironment provide biomarkers of immunotherapy options for patients with lung adenocarcinoma.Frontiers in genetics · 2022Article
- Epigenetic Regulation of Methylation in Determining the Fate of Dental Mesenchymal Stem Cells.Stem cells international · 2022Review
- Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers.Frontiers in oncology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor development involves alterations in DNA methylation patterns, which include both gains (hypermethylation) and losses (hypomethylation) in different genomic regions. The mechanisms underlying these two opposite, yet co-existing, alterations in tumors remain unclear. While studying the human MAGEA6/GABRA3 gene locus, we observed that DNA hypomethylation in tumor cells can lead to the activation of a long transcript (CT-GABRA3) that overlaps downstream promoters (GABRQ and GABRA3) and triggers their hypermethylation. Overlapped promoters displayed increases in H3K36me3, a histone mark deposited during transcriptional elongation and known to stimulate de novo DNA methylation. Consistent with such a processive mechanism, increases in H3K36me3 and DNA methylation were observed over the entire region covered by the CT-GABRA3 overlapping transcript. Importantly, experimental induction of CT-GABRA3 by depletion of DNMT1 DNA methyltransferase, resulted in a similar pattern of regional DNA hypermethylation. Bioinformatics analyses in lung cancer datasets identified other genomic loci displaying this process of coupled DNA hypo/hypermethylation, and some of these included tumor suppressor genes, e.g. RERG and PTPRO. Together, our work reveals that focal DNA hypomethylation in tumors can indirectly contribute to hypermethylation of nearby promoters through activation of overlapping transcription, and establishes therefore an unsuspected connection between these two opposite epigenetic alterations.
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