Objective: To 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.
Methods: 64 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.
Results: We 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.
Conclusions: A 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273419 | PMC |
| http://dx.doi.org/10.1016/j.ygyno.2006.03.045 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran.
Mol Biol Res Commun
January 2024
Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
To investigate the effects of 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of 3'UTR genotype with promoter methylation of and genes in CRC patients. The polymorphism of 3'UTR was evaluated through mutagenically specific PCR.
View Article and Find Full Text PDFDNA Mismatch Repair System Imbalances in Breast Adenocarcinoma.
Cancer Diagn Progn
March 2023
Breast Unit, 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
DNA mismatch repair system (MMR) is considered a leading genetic mechanism in stabilizing DNA structure and maintaining its function. DNA MMR is a highly conserved system in bacteria, prokaryotic, and eukaryotic cells, and provides the highest protection to DNA by repairing micro-structural alterations. DNA MMR proteins are involved in the detection and repair of intra-nucleotide base-to-base errors inside the complementary DNA strand recognizing the recently synthesized strand from the parental template.
View Article and Find Full Text PDFUpfront progression under pembrolizumab followed by a complete response after encorafenib and cetuximab treatment in BRAF V600E-mutated and microsatellite unstable metastatic colorectal cancer patient: A case report.
Genes Chromosomes Cancer
February 2022
Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris University; Assistance Publique-Hôpitaux de Paris, Paris, France.
Article Synopsis
- Two new treatment options have become standard for metastatic colorectal cancer patients, including encorafenib with cetuximab for specific BRAF V600E tumors and pembrolizumab for tumors with high microsatellite instability.
- There is a notable connection where about 30% of BRAF V600E mutated colorectal cancers are also identified as microsatellite unstable due to a specific genetic change.
- A unique case is reported of a patient with multiple mutations who initially progressed on pembrolizumab but experienced a rapid complete response after just two months of treatment with encorafenib and cetuximab during follow-up surgery.
The Frequency of DNA Mismatch Repair Deficiency Is Very Low in Surgically Resected Lung Carcinoma.
Front Oncol
October 2021
Department of Molecular Diagnostic Pathology, Iwate Medical University, Shiwa-gun, Japan.
Introduction: DNA mismatch repair (MMR) deficiency leads to changes in the length of nucleotide repeat sequences of tumor DNA. In that situation, DNA replicational errors occur and accumulate during DNA replication. As a result, this mechanism frequently affects the coding regions of oncogenes and tumor suppressor genes and causes carcinogenesis.
View Article and Find Full Text PDFEvaluation of biomarkers, genetic mutations, and epigenetic modifications in early diagnosis of pancreatic cancer.
World J Gastroenterol
September 2021
Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India.
Background: Pancreatic cancer (PC) is one of the deadliest malignancies with an alarming mortality rate. Despite significant advancement in diagnostics and therapeutics, early diagnosis remains elusive causing poor prognosis, marred by mutations and epigenetic modifications in key genes which contribute to disease progression.
Aim: To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!