ModificationsPromoterGuanineTransposable elementsNovo methylationTranscriptionCorrelatesMechanismsDNAmDeacetylasesDinucleotidesDifferentialMethyltransferasesPermissiveEukaryotesRegulateDNMT1DNMTsReproduciblePediatricTranscriptionallyProgressionGenomic regionsGeneticLociProteinsOccurGenesPatterns associatedDifferencesLungDiseasesSignaturesRegulationContrastCorrelationSitesRegionsMammalsAnalysisRoleCellLevelsUnderstoodExpression
Modifications5
- These epigenetic mechanisms are mediated by chemical modifications of DNA, proteins (most commonly histones), and RNA. (activemotif.com.cn)
- Key regulators that are essential for establishing and maintaining the epigenomic landscape are frequently mutated and can drive cancer development via alterations of DNA methylation and histone modifications [ 4 ]. (biomedcentral.com)
- Typically, transcriptional regulation is fine-tuned by epigenetic mechanisms, comprising histone modifications, DNA methylation, and non-coding RNAs (ncRNAs). (biomedcentral.com)
- 2 In addition to the well-established epigenetic role of DNA methylation, this definition includes a variety of more transient histone modifications such as acetylation, methylation, or phosphorylation that underlie epigenetic effects, and that will be discussed in this chapter along with the influence of SUMOylation, ubiquitination, adenosine diphosphate (ADP) ribosylation, and microRNA. (musculoskeletalkey.com)
- Also, more and more accumulating evidence indicates that the different histone modifications are strongly interconnected and can enforce or counteract each other. (musculoskeletalkey.com)
Promoter9
- The present study investigated the methylation of CpG sites in the cyclooxygenase (COX)‑2 promoter via nuclear factor (NF)‑κB transcriptional regulation and elucidated its effect on the COX‑2 transcriptional expression in a ketamine‑induced ulcerative cystitis (KIC) animal model. (spandidos-publications.com)
- Ketamine treatment increased the binding of NF‑κB and permissive histone H3 lysine‑4 (H3K4)m3, but caused a decrease in the repressive histone H3K27m3 and H3K36m3 on the COX‑2 promoter ranging from ‑1,522 to ‑1,331 bp as determined by a chromatin immunoprecipitation assay. (spandidos-publications.com)
- The mechanism of epigenetic regulation involves the CpG site methylation of promoter regions and the modification of DNA and histones by altering chromatin structure ( 9 - 11 ). (spandidos-publications.com)
- Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. (biomedcentral.com)
- Treating 293T cells with a histone deacetylase inhibitor increased acetylated histone H4 binding to the NR0B1 promoter and activated NR0B1 expression. (oncotarget.com)
- Furthermore, the level of acetyl-histone H4 binding to the NR0B1 promoter increased, whereas the occupancy of H3K27me3 was lower in cancerous tissues than in non-cancerous tissues. (oncotarget.com)
- In conclusion, this study shows that CpG methylation within the NR0B1 promoter is not involved in the in vivo regulation of NR0B1 expression, whereas the hyperacetylation of histone H4 and the unmethylation of histones H3K9 and H3K27, and their binding to the NR0B1 promoter results in decondensed euchromatin for NR0B1 activation. (oncotarget.com)
- Thus H3K9 methylation at the promoter region silences transcription, but within the coding region, H3K9 methylation was found to be associated with actively transcribed genes. (musculoskeletalkey.com)
- Expression of both isoforms negatively correlated with methylation at specific regions of the Mecp2 promoter, both at D2 and D8. (biomedcentral.com)
Guanine7
- The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. (wikipedia.org)
- The CpG notation is used to distinguish this single-stranded linear sequence from the CG base-pairing of cytosine and guanine for double-stranded sequences. (wikipedia.org)
- The CpG notation is therefore to be interpreted as the cytosine being 5 prime to the guanine base. (wikipedia.org)
- CpG should not be confused with GpC, the latter meaning that a guanine is followed by a cytosine in the 5' → 3' direction of a single-stranded sequence. (wikipedia.org)
- For example, in the human genome, which has a 42% GC content, a pair of nucleotides consisting of cytosine followed by guanine would be expected to occur 0.21 × 0.21 = 4.41 % {\displaystyle 0.21\times 0.21=4.41\%} of the time. (wikipedia.org)
- DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). (lookformedical.com)
- The most studied epigenetic marker type is DNA methylation (DNAm), which consists of the addition of a methyl group to cytosine residues within 5′-cytosine-phosphate-guanine-3′ dinucleotide sequences (known as 'CpG' sites). (biomedcentral.com)
Transposable elements2
- On the molecular level, it is well known that CpG methylation leads to X-chromosome inactivation, genomic imprinting, and suppression of transposable elements. (biomedcentral.com)
- We find that most sequence elements, including most classes of transposable elements, acquire methylation at similar rates overall. (biomedcentral.com)
Novo methylation2
- Given the predominant role of transcription, we sought to investigate whether transcription timing is rate limiting for de novo methylation and determines the asynchrony of methylation events. (biomedcentral.com)
- Although more highly transcribed genes acquire methylation earlier, the major transitions in the oocyte transcriptome occur well before the de novo methylation phase, indicating that transcription is generally not rate limiting in conferring permissiveness to DNA methylation. (biomedcentral.com)
Transcription7
- Moreover, in the ketamine group, the level of Ten‑Eleven‑Translocation methylcytosine dioxygenase for demethylation as determined by reverse transcription‑quantitative PCR assay was increased in comparison with the control group, but that was not the case for the level of DNA methyltransferases for methylation. (spandidos-publications.com)
- In contrast, treatment with histone methylase inhibitors decreased the methylation of histones H3K9 and H3K27 and slightly induced NR0B1 transcription. (oncotarget.com)
- In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established largely as a consequence of transcription events. (biomedcentral.com)
- We also identified differential enrichment of transcription factor binding motifs in CGIs acquiring methylation early or late in oocyte growth. (biomedcentral.com)
- As a result, there is highly programmed methylation of a defined set of ~2000 CGIs in oocytes, mostly on account of their location within active transcription units. (biomedcentral.com)
- It is generally believed that the histone code can influence transcriptional activity directly by affecting chromatin structure, thereby making it more or less accessible for transcription factors and indirectly leading to the attraction of effector molecules that in turn recruit and stabilize the transcription machinery. (musculoskeletalkey.com)
- HDACs and HATs not only modify histones, they also form complexes with transcription factors, oncoproteins, and tumor suppressors and regulate their activity by changing the acetylation status. (musculoskeletalkey.com)
Correlates1
- Instead, CGI methylation timing negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin remodelling as a major determinant of methylation timing. (biomedcentral.com)
Mechanisms2
- We hypothesize that CDCA7 becomes dispensable in species that lost HELLS or DNA methylation, and/or the loss of CDCA7 triggers the replacement of DNA methylation by other chromatin regulation mechanisms. (elifesciences.org)
- therefore, it provides a unique opportunity to investigate the extent to which different sequence features acquire methylation as a result of common or distinct mechanisms. (biomedcentral.com)
DNAm2
- Since methylation is also associated with genetic ancestry [ 17 ], we hypothesize that differential DNAm patterns in whole blood may contribute to the differences in lung function among Puerto Ricans and Mexicans. (biomedcentral.com)
- DNA methylation (DNAm) may mediate these effects. (bvsalud.org)
Deacetylases1
- Histone acetylation is catalyzed by histone acetyltransferases (HATs) and is counteracted by histone deacetylases (HDACs). (musculoskeletalkey.com)
Dinucleotides2
- Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. (wikipedia.org)
- Methylation of cytosine (5 mC) residues in CpG dinucleotides across the genome is an epigenetic modification that plays a pivotal role in the establishment of cellular identity by influencing gene expression during development [ 1 ]. (biomedcentral.com)
Differential2
- Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. (biomedcentral.com)
- Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status. (biomedcentral.com)
Methyltransferases1
- Moreover, the CpG site methylation is mediated by DNA methyltransferases (DNMTs), which catalyze the addition of a methyl group to cytosine ( 13 , 14 ). (spandidos-publications.com)
Permissive1
- These results do not support a major role for transcriptional transitions in the time of onset of DNA methylation in the oocyte, but suggest a model in which sequences least dependent on chromatin remodelling are the earliest to become permissive for methylation. (biomedcentral.com)
Eukaryotes3
- In addition to RNA-associated silencing and histone modification, a major epigenetic mechanism in higher-order eukaryotes is DNA methylation. (qiagen.com)
- The results suggest that the roles for the two factors in DNA methylation maintenance pathways can be traced back to the last eukaryotic common ancestor and that the CDC7A-HELLS-DNMT axis shaped the evolutionary retention of DNA methylation in eukaryotes. (elifesciences.org)
- DNA methylation, particularly 5-methylcytosine (5mC) at CpG sequences, is widely conserved in eukaryotes. (elifesciences.org)
Regulate1
- In contrast, the Ten-Eleven-Translocation (TET) dioxygenase family, including TET1, TET2 and TET3, mediates active DNA demethylation and hydroxylate-methylated DNA by converting 5-methylcyto-sine to 5-hydroxymethylcytosine to regulate DNA methylation status. (spandidos-publications.com)
DNMT12
- DNMT1 preserves the methyltransferase by binding to hemi-methylated CpG sites and methylates the cytosine on the newly synthesized strand after DNA replication, whereas DNMT3a/DNMT3b are required for the de novo genomic methylation of DNA ( 15 ). (spandidos-publications.com)
- In animals, 5mC is maintained during DNA replication by DNMT1 together with UHRF1, which directly recognizes hemimethylated cytosine via the SRA domain and stimulates activity of DNMT1 in a manner dependent on its ubiquitin-ligase activity ( Nishiyama and Nakanishi, 2021 ). (elifesciences.org)
DNMTs2
- Maintenance DNMTs (directly or indirectly) recognize hemimethylated CpGs and restore symmetric methylation at these sites to prevent the passive loss of 5mC upon DNA replication. (elifesciences.org)
- Conversely, methylation by de novo DNMTs does not require methylated DNA templates. (elifesciences.org)
Reproducible2
- QIAseq Targeted Methyl Panels deliver high mapping efficiency (figure QIAseq Targeted Methyl Panel: mapping efficiency Input >1 ng – gDNA – FFPE – ccfDNA Results show high mapping on primer and high unique mapping. "> QIAseq Targeted Methyl Panel: mapping efficiency ), high reproducibility (figure QIAseq Targeted Methyl Panel: methylation degree reproducibility To test methylation degree accuracy and reproducibility, 40 ng control DNA with 0%, 50% and 100% methylation were processed using the QIAseq Targeted Methyl Panel, which consisted of 749 primers. Samples were sequenced on MiSeq and methylation degree of CpG covered by >30 UMI was evaluated, resulting in accurate and highly reproducible methylation calling. "> QIAseq Targeted Methyl Panel: methylation degree reproducibility ) and high correlation with established methods (figures QIAseq Targeted Methyl Panel - high correlation with established methods To test correlation with established methods, the QIAseq Targeted Methyl Panel was used with 40 ng input gDNA from hepatocytes. The panel consisted of 102 primers, covering 71 CpGs. Compared to the Supplier I array, methylation degree resulted in high correlation. "> QIAseq Targeted Methyl Panel - high correlation with established methods and QIAseq Targeted Methyl Panel: methylation status of FFPE DNA: methylation degree To test methylation status of FFPE DNA, the QIAseq Targeted Methyl Panel was used with 40 ng input FFPE DNA. The panel consisting of 93 primers covered 566 CpG sites. The evaluated methylation degree of 7 CpG sites of the MGMT gene highly correlates to the methylation degree that was previously validated with Pyrosequencing. "> QIAseq Targeted Methyl Panel: methylation status of FFPE DNA: methylation degree ). (qiagen.com)
- However, methylation of CpG islands (CGIs) is delayed compared with the genome average and there are reproducible differences amongst CGIs in onset of methylation. (biomedcentral.com)
Pediatric2
- In the present study we provide a comprehensive, genome-wide map of de novo DNA methylation changes in ALL cells at diagnosis and relapse by interrogating the methylation levels of 435,941 CpG sites distributed genome-wide in a large collection of pediatric ALL cells of diverse cytogenetic backgrounds. (biomedcentral.com)
- Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos. (biomedcentral.com)
Transcriptionally1
- However, whether and how DNMT targets specific gene loci, and induces transcriptionally relevant changes in DNA methylation signatures that elicit physiological responses, is not fully understood. (biomedcentral.com)
Progression2
- Therefore, we generated genome-wide methylation and transcriptome maps of size-selected, growing oocytes to capture the onset and progression of methylation. (biomedcentral.com)
- Recent findings suggest that DNA methylation changes are related to the development and progression of a group of human diseases including atherosclerosis. (biomedcentral.com)
Genomic regions1
- DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. (biomedcentral.com)
Genetic2
- Mutations in HELLS, its activator CDCA7, and the de novo DNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. (elifesciences.org)
- A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. (biomedcentral.com)
Loci1
- however, little is known about the kinetics of methylation gain genome wide and the reasons for asynchrony in methylation at imprinted loci. (biomedcentral.com)
Proteins1
- The best studied effector proteins binding phosphorylated histones are 14-3-3 proteins and BRCA1 C-terminus (BRCT) domains. (musculoskeletalkey.com)
Occur1
- Cytosine methylation may also occur in non-CpG content, as described for embryonic stem cells. (qiagen.com)
Genes1
- We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD. (biomedcentral.com)
Patterns associated1
- At different stages of NSC differentiation, Mecp2 isoforms showed reciprocal expression patterns associated with minor, but significant changes in DNA methylation at the Mecp2 REs. (biomedcentral.com)
Differences1
- Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment. (biomedcentral.com)
Lung1
- The association between different methylation patterns and lung function can be analyzed with epigenome-wide association studies (EWAS). (biomedcentral.com)
Diseases1
- Disruption of DNA methylation patterns is associated with diseases, and particularly with cancer [ 3 ]. (biomedcentral.com)
Signatures2
- This survey uncovered four characteristic methylation signatures. (biomedcentral.com)
- This important manuscript reveals signatures of co-evolution of two nucleosome remodeling factors, Lsh/HELLS and CDCA7, which are involved in the regulation of eukaryotic DNA methylation. (elifesciences.org)
Regulation2
- Methylating the cytosine within a gene can change its expression, a mechanism that is part of a larger field of science studying gene regulation that is called epigenetics. (wikipedia.org)
- Hence, we here propose a triple helix recognition mechanism, underlying cell motility regulation via lncRNA-targeted DNA methylation in a clinically relevant context. (biomedcentral.com)
Contrast1
- In contrast, decitabine withdrawal downregulated both Mecp2 isoforms to different extents at D8, without affecting DNA methylation at the Mecp2 REs. (biomedcentral.com)
Correlation2
- Further, we performed correlation analysis between DNA methylation at the Mecp2 REs and the expression of Mecp2 isoforms after decitabine exposure and withdrawal. (biomedcentral.com)
- Our results show the correlation between the expression of Mecp2 isoforms and DNA methylation in differentiating NSC, providing insights on the potential role of DNA methylation at the Mecp2 REs in Mecp2 isoform-specific expression. (biomedcentral.com)
Sites1
- We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. (biomedcentral.com)
Regions2
- DNA methylation occurs on cytosine residues, especially in CpG islands, which are GC-rich regions. (qiagen.com)
- Finally, we show that establishment of non-CpG methylation, which is prevalent in fully grown oocytes, and methylation over non-transcribed regions, are later events in oogenesis. (biomedcentral.com)
Mammals1
- In mammals, 70% to 80% of CpG cytosines are methylated. (wikipedia.org)
Analysis1
- ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing. (biomedcentral.com)
Role2
- Methylation of CpG islands is known to inactivate gene expression and plays an important role in normal and disease development. (qiagen.com)
- Our study suggests that a unique specialized role of CDCA7 in HELLS-dependent DNA methylation maintenance is broadly inherited from the last eukaryotic common ancestor. (elifesciences.org)
Cell1
- We used a previously characterized in vitro differentiating neural stem cell (NSC) system to investigate the interplay between Mecp2 isoform-specific expression and DNA methylation at the Mecp2 REs. (biomedcentral.com)
Levels2
- DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples. (biomedcentral.com)
- DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity. (biomedcentral.com)
Understood2
- The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood. (biomedcentral.com)
- However, the genome-wide DNA methylation patterns have not yet been comprehensively described for all subtypes of ALL and the synergy between DNA methylation, leukemogenesis, drug resistance, and relapse in ALL is poorly understood. (biomedcentral.com)
Expression3
- Similar histone occupancies were confirmed in a comparison of cancerous tissues with strong, moderate and negative NR0B1 expression. (oncotarget.com)
- This mediates DNA methylation-dependent silencing of Ncam1 , being abolished by ephrinA5 stimulation-triggered reduction of Snhg15 expression. (biomedcentral.com)
- We hypothesized that DNA methylation at these REs may impact the expression of Mecp2 isoforms. (biomedcentral.com)