ArticleMolecular and cellular biology2003
Methylation of adjacent CpG sites affects Sp1/Sp3 binding and activity in the p21(Cip1) promoter.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.
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Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Aryl hydrocarbon receptor gene transitions (c.-742C>T; c.1661G>A) and idiopathic male infertility: a case-control study with in silico and meta-analysis.Environmental science and pollution research international · 2017Pooled it
- Integrated multi-omics profiling uncovers the epigenetic, transcriptional, and metabolic landscape of prostate cancer progression.BMC cancer · 2026Article
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- DNA methylation as an epigenetic mechanism in the regulation of LEDGF expression and biological response in aging and oxidative stress.Cell death discovery · 2024Article
- DNA methylation alterations at RE1-silencing transcription factor binding sites and their flanking regions in cancer.Clinical epigenetics · 2023Article
- Limb blastema formation: How much do we know at a genetic and epigenetic level?The Journal of biological chemistry · 2023Review
- Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage.Frontiers in cell and developmental biology · 2023Article
- Prediction of the Effect of Methylation in the Promoter Region of ZP2 Gene on Egg Production in Jinghai Yellow Chickens.Veterinary sciences · 2022Article
- The Epigenetics of Psychosis: A Structured Review with Representative Loci.Biomedicines · 2022Review
- The concurrence of DNA methylation and demethylation is associated with transcription regulation.Nature communications · 2021Article
- Epigenetic down-regulation of microRNA-126 in scleroderma endothelial cells is associated with impaired responses to VEGF and defective angiogenesis.Journal of cellular and molecular medicine · 2021Article
- Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes.Diabetologia · 2020Article
- Stearoyl-CoA desaturase (Epigenetics · 2020Article
- Epigenetics in age-related macular degeneration: new discoveries and future perspectives.Cellular and molecular life sciences : CMLS · 2020Review
- Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia.Human genomics · 2020Article
- A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer.Cancer cell international · 2020Article
- Relationship between Mental Health, theBioMed research international · 2020Article
- The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- Ethnic and Adipose Depot Specific Associations Between DNA Methylation and Metabolic Risk.Frontiers in genetics · 2020Article
- Cross-Sectional Survey of Mental Health Risk Factors and Comparison of theInternational journal of environmental research and public health · 2019Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
DNA methylation in the promoter of certain genes is associated with transcriptional silencing. Methylation affects gene expression directly by interfering with transcription factor binding and/or indirectly by recruiting histone deacetylases through methyl-DNA-binding proteins. In this study, we demonstrate that the human lung cancer cell line H719 lacks p53-dependent and -independent p21(Cip1) expression. p53 response to treatment with gamma irradiation or etoposide is lost due to a mutation at codon 242 of p53 (C-->W). Treatment with depsipeptide, an inhibitor of histone deacetylase, was unable to induce p53-independent p21(Cip1) expression because the promoter of p21(Cip1) in these cells is hypermethylated. By analyzing luciferase activity of transfected p21(Cip1) promoter vectors, we demonstrate that depsipeptide functions on Sp1-binding sites to induce p21(Cip1) expression. We hypothesize that hypermethylation may interfere with Sp1/Sp3 binding. By using an electrophoretic mobility shift assay, we show that, although methylation within the consensus Sp1-binding site did not reduce Sp1/Sp3 binding, methylation outside of the consensus Sp1 element induced a significant decrease in Sp1/Sp3 binding. Depsipeptide induced p21(Cip1) expression was reconstituted when cells were pretreated with 5-aza-2'-deoxycytidine. Our data suggest, for the first time, that hypermethylation around the consensus Sp1-binding sites may directly reduce Sp1/Sp3 binding, therefore leading to a reduced p21(Cip1) expression in response to depsipeptide treatment.
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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.