Cytosine methylation is a key mechanism of epigenetic regulation. CpG-dense loci, called "CpG islands", play a particularly important role in modulating gene expression. Methylation has long been suspected to alter the physical properties of DNA, but the full spectrum of the evoked changes is unknown. Here we measured the methylation-induced nanomechanical changes in a DNA molecule with the sequence of a CpG island. For the molecule under tension, contour length, bending rigidity and intrinsic stiffness decreased in hypermethylated dsDNA, pointing at structural compaction which may facilitate DNA packaging in vivo. Intriguingly, increased forces were required to convert hypermethylated dsDNA into an extended S-form configuration. The reduction of force hysteresis during mechanical relaxation indicated that methylation generates a barrier against strand unpeeling and melting-bubble formation. The high structural stability is likely to have significant consequences on the recognition, replication, transcription, and reparation of hypermethylated genetic regions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300791 | PMC |
| http://dx.doi.org/10.1016/j.bpj.2016.12.029 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.
Science
July 2024
Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston MA, USA.
Article Synopsis
- The gene IDH1 often changes in many cancers, leading to a harmful substance that messes with the body's natural defenses.
- Tumors with this change often keep immune cells out, but blocking the mutant IDH1 can help the body's immune system attack the cancer.
- The study shows that the mutant IDH1 silences certain genes that would usually help the immune system work, but stopping this mutation can help reactivate those genes and boost immunity against tumors.
Hypermethylated genome of a fish vertebrate iridovirus ISKNV plays important roles in viral infection.
Commun Biol
February 2024
State Key Laboratory for Biocontrol, Southern Laboratory of Ocean Science and Engineering (Zhuhai), Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang Bay, Guangdong Province Key Laboratory of Aquatic Economic Animals, School of Marine Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
Article Synopsis
- - Iridoviruses are large DNA viruses that infect both invertebrates and cold-blooded vertebrates, with their unique hypermethylated genomes still not fully understood.
- - The study focuses on the Infectious spleen and kidney necrosis virus (ISKNV), finding that its methylation level is 23.44%, crucial for viral replication but not for gene expression.
- - Results show that hypomethylated ISKNV boosts immune responses, indicating that increased methylation might help the virus evade the immune system, shedding light on the role of genome methylation in viral infections.
Hybridization-based CpG methylation level detection using methyl-CpG-binding domain-fused luciferase.
Anal Bioanal Chem
May 2023
Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakuramachi, Hachioji, Tokyo, 192-0982, Japan.
Hypermethylation of tumor-suppressor genes and global hypomethylation, which is related to methylation level at the retroelement, have been recognized as features of the cancer genome. In this study, we developed a hybridization-based CpG methylation level detection method using methyl-CpG-binding domain-fused firefly luciferase (MBD-Fluc). In this method, methylated probe oligonucleotides were used to capture target oligonucleotides.
View Article and Find Full Text PDFA new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma.
Cell Biosci
December 2022
Department of Special Clinic, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China.
Rationale: Recent research has indicated that cuprotosis, or copper induced cell death, is a novel type of cell death that could be utilized as a new weapon for cancer management. However, the characteristics and implications of such signatures in cancers, especially in clear cell renal cell cancer (ccRCC), remain elusive.
Methods: Expression, methylation, mutation, clinical information, copy number variation, functional implication, and drug sensitivity data at the pan-cancer level were collected from The Cancer Genome Atlas.
Tribbles 2 mediates cisplatin sensitivity and DNA damage response in epithelial ovarian cancer.
Int J Cancer
October 2017
Department of Gynecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany.
Aim was to identify methylated genes with functional involvement in cisplatin-resistance development of epithelial ovarian cancer (EOC). Genome-wide analyses of hypermethylated CpG-islands in resistant cell lines in combination with qRT-PCR analyses were used to identify epigenetically silenced genes. EOC-Type-II tumors were analyzed for gene methylation and expression and TCGA data were interrogated in-silico.
View Article and Find Full Text PDFWant 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!