ArticleGynecologic oncology2006
hMLH1 promoter methylation and silencing in primary endometrial cancers are associated with specific alterations in MBDs occupancy and histone modifications.
Article in Gynecologic oncology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- 17beta-estradiol (E2) Regulates Malignancies and Stemness in Endometrial Carcinoma (EC) via Interacting with ESR1.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Research Progress of DNA Methylation Markers for Endometrial Carcinoma Diagnosis.Journal of Cancer · 2025Review
- Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review.Frontiers in genetics · 2023Review
- Research Progress of DNA Methylation in Endometrial Cancer.Biomolecules · 2022Review
- MBD2 as a novel marker associated with poor survival of patients with hepatocellular carcinoma after hepatic resection.Molecular medicine reports · 2016Article
- Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons.Gynecologic oncology · 2015Article
- hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases.Clinical & experimental metastasis · 2012Article
- Article
- Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promoter.Molecular and cellular biology · 2011Article
- Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium.Toxicology and applied pharmacology · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
objectiveTo investigate the relationship between hMLH1 promoter methylation and changes in chromatin composition. To study how the occupancy of methyl CpG binding domain proteins (MBDs) and histone acetylation/methylation in hMLH1 promoter may participate in hMLH1 silencing.
methods64 endometrial cancer samples were screened for hMLH1 mRNA expression. hMLH1 promoter methylation status was confirmed by methylation-specific PCR in cancers with high and low levels of hMLH1 expression. Chromatin immunoprecipitation was performed to compare the MBD occupancy and histone modifications between the methylated/silenced and unmethylated/active hMLH1 genes in multiple primary endometrial cancers.
resultsWe demonstrated that MeCP2, MBD1 and MBD2, but not MBD3 and MBD4, specifically bind to methylated hMLH1 promoters. Hyperacetylated histones H3 and H4 were found to be associated with the unmethylated and transcriptionally active hMLH1 promoters. While H3 lysine-4 methylation was present in unmethylated hMLH1 promoters, H3 lysine-9 methylation was found exclusively in methylated promoters. Western blot analysis showed that similar global levels of MBDs and histones were present in the two cancer groups with high and low hMLH1 expression.
conclusionsA distinct combination of MBDs and histone modification is associated with the silencing of the hMLH1 gene. The changes in hMLH1 chromatin composition are closely related to methylation status of hMLH1 promoters. These changes are not accounted by the global expression levels of MBDs and histones in endometrial cancers.
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