ArticlePloS one2011
Long term transcriptional reactivation of epigenetically silenced genes in colorectal cancer cells requires DNA hypomethylation and histone acetylation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Hypermethylation of protocadherin γ subfamily A12 and solute carrier family 19 A 1 promoters contributes to the occurrence and metastasis of colorectal cancer.Oncology letters · 2018Article
- The Role of Stem Cell DNA Methylation in Colorectal Carcinogenesis.Stem cell reviews and reports · 2016Review
- Epigenetic regulation of the novel tumor suppressor cysteine dioxygenase 1 in esophageal squamous cell carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Silencing of the DNA mismatch repair gene MLH1 induced by hypoxic stress in a pathway dependent on the histone demethylase LSD1.Cell reports · 2014Article
- Epigenetic biomarkers: potential applications in gastrointestinal cancers.ISRN gastroenterology · 2014Review
- Identification of a class of human cancer germline genes with transcriptional silencing refractory to the hypomethylating drug 5-aza-2'-deoxycytidine.Oncoscience · 2014Article
- Effect of dynamic DNA methylation and histone acetylation on cPouV expression in differentiation of chick embryonic germ cells.Stem cells and development · 2013Article
- Vorinostat in combination with bortezomib in patients with advanced malignancies directly alters transcription of target genes.Cancer chemotherapy and pharmacology · 2013Article
- Frequent inactivation of cysteine dioxygenase type 1 contributes to survival of breast cancer cells and resistance to anthracyclines.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Methylation kinetics and CpG-island methylator phenotype status in colorectal cancer cell lines.Biology direct · 2013Article
- Article
- Valproic acid shows a potent antitumor effect with alteration of DNA methylation in neuroblastoma.Anti-cancer drugs · 2012Article
- Article
- Epigenetic changes in pediatric solid tumors: promising new targets.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Review
- Valproic acid overcomes hypoxia-induced resistance to apoptosis.Oncology reports · 2012Article
- Mining gene expression signature for the detection of pre-malignant melanocytes and early melanomas with risk for metastasis.PloS one · 2012Article
- Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers.PloS one · 2012Article
- Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer.PloS one · 2012Article
- Tamoxifen-induced epigenetic silencing of oestrogen-regulated genes in anti-hormone resistant breast cancer.PloS one · 2012Article
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2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledEpigenetic regulation of genes involves the coordination of DNA methylation and histone modifications to maintain transcriptional status. These two features are frequently disrupted in malignancy such that critical genes succumb to inactivation. 5-aza-2'-deoxycytidine (5-aza-dC) is an agent which inhibits DNA methyltransferase, and holds great potential as a treatment for cancer, yet the extent of its effectiveness varies greatly between tumour types. Previous evidence suggests expression status after 5-aza-dC exposure cannot be explained by the DNA methylation status alone.
aimWe sought to identify chromatin changes involved with short and long term gene reactivation following 5-aza-dC exposure. Two colorectal cancer cell lines, HCT116 and SW480, were treated with 5-aza-dC and then grown in drug-free media to allow DNA re-methylation. DNA methylation and chromatin modifications were assessed with bisulfite sequencing and Chromatin Immuno-Precipitation analysis.
resultsIncreased H3 acetylation, H3K4 tri-methylation and loss of H3K27 tri-methylation were associated with reactivation. Hypermethylated genes that did not show increased acetylation were transiently expressed with 5-aza-dC treatment before reverting to an inactive state. Three reactivated genes, CDO1, HSPC105 and MAGEA3, were still expressed 10 days post 5-aza-dC treatment and displayed localised hypomethylation at the transcriptional start site, and also an increased enrichment of histone H3 acetylation.
conclusionsThese observations suggest that hypomethylation alone is insufficient to reactivate silenced genes and that increased Histone H3 acetylation in unison with localised hypomethylation allows long term reversion of these epigenetically silenced genes. This study suggests that combined DNA methyltransferase and histone deacetylase inhibitors may aid long term reactivation of silenced genes.
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