Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. was achieved specifically through Tet3-mediated hydroxymethylation. Collectively our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse kidney fibrosis. In recent years epigenetics have emerged as determinants of fibrosis in the kidney (and other tissues as well).1-5 Furthermore epigenetics have been implied to contribute to the individual susceptibilities of CKD patients to develop fibrosis.1-3 Among the known epigenetic mechanisms methylation of CpG island promoters (referred to as DNA methylation) is the most potent to silence transcription of affected genes.6 Because transcriptional silencing of affected genes has been shown to causally contribute to fibroblast activation and Sapitinib fibrogenesis inhibition or reversal of such aberrant methylation is considered beneficial for the kidney.3 Although in ...
CpG island hypermethylation is an epigenetic control aberration that is important for gene inactivation in cancer cells. Hypermethylation of CpG islands has been described in almost every type of tumor. Many important cellular pathways, such as DNA repair (hMLH1, for example), cell cycle (p14ARF), apoptosis (DAPK), cell adherence (CDH1, CDH13), are inactivated by this epigenetic lesion. Hypermethylation is linked to methyl-binding proteins, DNA methyltransferases and histone deacetylase, but the degree to which this process selectively silences tumor suppressor genes continues to remain a vibrant field of study. The list for hypermethylated genes is growing and functional and genetic studies are being performed to determine which hypermethylation events are relevant for tumorigenesis. Basic as well as translational research will be needed to understand the mechanisms and roles of CpG island hypermethylation in cancer. The first discovery of methylation in a CpG island of a tumor suppressor gene ...
TY - JOUR. T1 - Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma. AU - van Vlodrop, Iris J. H.. AU - Baldewijns, Marcella M. L.. AU - Smits, Kim M.. AU - Schouten, Leo J.. AU - van Neste, Leander. AU - Van Criekinge, Wim. AU - van Poppel, Hein. AU - Lerut, Evelyne. AU - Schuebel, Kornel E.. AU - Ahuja, Nita. AU - Herman, James G.. AU - de Bruine, Adriaan P.. AU - van Engeland, Manon. PY - 2010/2. Y1 - 2010/2. U2 - 10.2353/ajpath.2010.090442. DO - 10.2353/ajpath.2010.090442. M3 - Article. VL - 176. SP - 575. EP - 584. JO - American Journal of Pathology. JF - American Journal of Pathology. SN - 0002-9440. IS - 2. ER - ...
CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in HCC. We examined the promoter methylation status of 9 genes associated with telomerase activity in 120 HCC, 120 cirrhosis tissues and 10 normal liver tissues by methylation-specific PCR. Assay of telomerase activity was by TRAP-ELISA. The frequency of promoter methylation of each gene was P21 63.3%, P15 42.5%, P16 62.5%, P53 14.2%, RB 32.5%, P27 48.3%, WTI 54.2%, E2F-1 70.8% and P300 65.8% of 120 HCC. Methylation status of P21, P15, P16, WTI and E2F-1 was significantly associated with HCC and nontumor tissues (p | 0.05). CIMP+ was detected in 61.7% (74/120) HCC and 15% (18/120) cirrhosis tissues, no CIMP+ was present in normal liver tissues (p | 0.001).
Previous studies of hypermethylation in Barretts esophagus and EAC have been limited to the CDKN2A gene and have focused on the analysis of a very small number of samples from each patient with Barretts esophagus and/or esophageal adenocarcinoma. In this study, we have used an alternative approach that not only documents the occurrence of hypermethylation of four CpG islands (APC, CDH1, CDKN2A, and ESR1) but also provides the topological context in which this hypermethylation occurs in histologically defined areas of Barretts-associated EAC. Because this experimental approach by necessity involves the analysis of a large number of samples per patient, we have restricted the number of cases to six. Although the limited number of patients does not allow us to extrapolate on the general occurrence of hypermethylation of these four genes in Barretts-associated EAC, this alternative strategy revealed interesting trends.. Our results demonstrate two important points:. (a) Abnormal methylation ...
Restriction landmark genomic scanning (RLGS) has been used to study aberrant CpG island methylation in cancer for more than ten years. This approach remains one of the most reliable ways to characterize CpG island hypermethylation in cancer and has been used both to characterize differences in aberrant methylation phenotypes and also to identify tumor suppressor genes. Not only have known tumor suppressor genes like Cdkn2a (p16), Itga4 (α 4-integrin) [1], and Igfbp7 [2] been identified as targets of aberrant methylation in cancer by RLGS, but also novel tumor suppressor genes such as TCF21 [3], SLC5A8 [4], ID4 [5], BMP3B [6], and SOCS1 [7] have been identified by RLGS.. RLGS is a two-dimensional gel electrophoresis method [8] that allows detection of DNA methylation if a methylation sensitive landmark enzyme such as NotI is used. Up to 2,000 end-labeled landmark sites are displayed in a single RLGS profile. The labeling of the sites is based on incorporation of radionucleotides into the NotI ...
Aberrant CpG methylation changes occurring during tumour progression include the loss (hypomethylation) and gain (hypermethylation) of methyl groups. control. We have therefore demonstrated the ability of this technique, the identification of CGI exhibiting altered methylation patterns (ICEAMP), to isolate tumour-specific methylated GC-rich sequences. This will allow a comprehensive identification of methylation changes during tumourigenesis and will lead to a better understanding of the processes involved. INTRODUCTION The aberrant methylation of CpG dinucleotides has been widely reported during tumourigenesis in a variety of cancers (for review see 1). The alterations identified and their consequences include the loss of methyl groups, which is thought to buy 931409-24-4 increase chromosomal instability (2). Alternatively, the gain of methyl groups, particularly in CpG islands [CGIs: GC-rich regions of the genome, ~1 kb in length, originally characterised due to their lack of methylation (3)], ...
The methylator phenotype (CIMP) in CRC was identified by Toyota and colleagues after selecting particular CpG islands (CpGis) that displayed methylation in cancer-specific manner (so-called MINT loci; ref. 2). This allowed to distinguish subgroups of CRCs with prominent number of methylated CpGis, specific molecular features (BRAF mutation and MSI), and preferential localization in the proximal colon (later called CIMP-high or CIMP1; refs. 1, 2). Subsequently, after screening methylation of 92 CpGis in 187 CRCs, a new CIMP-specific marker panel was proposed by Weisenberger and colleagues and further enriched with new markers by Ogino and colleagues (3, 4). Parallel to the searches for marker candidates, a subgroup of CRCs with less extensive CpGis methylation enriched for the KRAS mutants was revealed (CIMP-low or CIMP2; refs. 7, 29). Finally, non-CIMP tumors (CIMP-0) have been correlated with a frequent loss of heterozygosity (LOH) at 18q that is regarded as 1 of the signs of chromosomal ...
The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in normal cells. At present, it is also clear that DNA methylation forms an important part of the normal cell-regulatory processes that govern gene transcription. Methylation, targeted at CpG islands, is an important part of the mechanisms that govern X-chromosome inactivation; it is also essential for the maintenance of imprinted genes and, at least in some cases, is critical in determining the cell-type-specific expression patterns of genes. Study of these examples will be important in identifying the mechanisms that control targeting of DNA methylation and how these processes are disrupted during disease pathogenesis.. ...
The effect of CpG islands on transgene expression was first tested in cultured cells. In transient transfection it was demonstrated that CpG islands do not influence the expression of a transgene when not integrated into the genome. Even when integrated into the genome of cultured cells, CpG islands are not able to confer position-independent, copy number-dependent transgene expression, as confirmed by the analysis of individual cell lines. However, the results from bulk analysis of primary clones suggest that CpG islands improve the level of expression in cultured cells, and increase the proportion of highly expressing clones. Transgenic mice were used to study the effect of CpG islands on the level and pattern of transgene expression in vivo. Unexpectedly, from the nine transgenic lines generated, transgene expression was detected in only one line. In the rest of the lines transgene expression was silenced, and in these cases the transgene was densely methylated. In half of the silenced lines ...
Precise mapping of DNA methylation patterns in CpG islands has become essential for understanding diverse biological processes such as the regulation of imprinted genes, X chromosome inactivation, and tumor suppressor gene silencing in human cancer. We describe a new method, MSP (methylation-specific PCR), which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes. This assay entails initial modification of DNA by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequent amplification with primers specific for methylated versus unmethylated DNA. MSP requires only small quantities of DNA, is sensitive to 0.1% methylated alleles of a given CpG island locus, and can be performed on DNA extracted from paraffin-embedded samples. MSP eliminates the false positive results inherent to previous PCR-based approaches which relied on differential ...
Inactivaion of tumor suppressor genes (TSGs) by promoter CpG methylation frequently occurs in tumorigenesis, even in the early stages, contributing to the initiation and progression of human cancers. Deleted in lung and esophageal cancer 1 (DLEC1), located at the 3p22-21.3 TSG cluster, has been identified frequently silenced by promoter CpG methylation in multiple carcinomas, however, no study has been performed for lymphomas yet. We examined the expression of DLEC1 by semi-quantitative reverse transcription (RT)-PCR, and evaluated the promoter methylation of DLEC1 by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) in common lymphoma cell lines and tumors. Here we report that DLEC1 is readily expressed in normal lymphoid tissues including lymph nodes and PBMCs, but reduced or silenced in 70% (16/23) of non-Hodgkin and Hodgkin lymphoma cell lines, including 2/6 diffuse large B-cell (DLBCL), 1/2 peripheral T cell lymphomas, 5/5 Burkitt, 6/7 Hodgkin and 2/3 nasal killer (NK)/T-cell
CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole.. The unmasked version of the track displays potential ...
CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole.. The unmasked version of the track displays potential ...
The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. The causes of CIMP are unknown. We studied CIMP in hyperplastic polyps (HPs), with emphasis on patients with multip …
Another question, if a 200bp fragment of CpG island across part of promoter and part of exon1, does its methylation state could be representative the methylation state of the whole promter CpG islands(more than 1000bp long)? Does it necessary to detect methylation state of the whole promoter CpG islands? If not, which region is the best representative? And how to find it? For MSP method,how long fragment is appropriate for detection ...
Results The frequency of promoter methylation was 52% for p14, 44% for p15, 50% for p16, 56% for p21, 38% for p27, 8% for p53, 42% for p57, 36% for p73, and 44% for RB1 of 50 ESCC. CIMP+ was detected in 54% (27/50) of ESCC and 8% (4/50) of dysplastic tissues; no CIMP+ was present in normal epithelial tissues (p,0.001). The results show that promoter methylation of p14, p15, p16, p21, p27, p57 and p73 was far more common in ESCC samples with CIMP+ than those with CIMP−. A significant difference between CIMP status and TNM stage and metastasis was found in ESCC (p,0.05). Patients with ESCC with CIMP+ had poorer 4-year survival than those with CIMP−. ...
Over the past few years a considerable number of studies have been made on DNA methylation. It is vital in establishing, defining, or stabilizing the various cell types in the developing embryo and associated with transcriptional silencing of genes on the inactive X chromosome, imprinted genes and increased risk of cancer because of abnormal DNA methylation in the genome. CpG islands hypermethylation is an epigenetic event that does not involve changes in nucleotide sequences. A comprehensive understanding of epigenetic events in basic research of mouse models is necessary to establish an array-based strategy. The mouse CpG islands microarray, mCGI microarray, is a new dual functional high-throughput screening of CpG island tags and gene expressions in the mouse genome. The mCGI microarray contains 2304 CpG islands, 28 control genes (including imprinting genes and tumor suppressor genes) and 10 internal control genes (clones without restriction cut sites and their copy numbers remain the same in ...
Mechanisms regulating mitochondrial DNA (mtDNA) amount according to developmental stage and tissue origin are still unknown. Recent works have suggested the role of epigenetic modification at a CpG island located in POLG gene, encoding the polymerase responsible for mtDNA synthesis. We found that this CpG island is highly methylated in human tissues, whatever developmental stages (after 12 weeks) or tissue energy-demand. This methylation level is not modified by the presence of genetic mutations that can alter the mtDNA amount (mtDNA or inactivating POLG mutations). Mechanisms involved in mtDNA amount control in human differenciated cells remain to be identified. (By Dr. Julie STEFFANN, http://jmg.bmj.com/content/early/2017/01/09/jmedgenet-2016-104335 ...
BACKGROUND: Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profiles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations ...
There are so many CpG sites in one CpG island ,and the CpG sites investigated by a MSP are so limited. Only less than 10 CpG sites included in the two pairs of primers for MSP that can be investgated by a MSP. Why so little CpG sites mehtylation informatiom can repsent the whole CpG island ...
The evaluation of a large, population-based sample strongly supports the biologic relevance of CIMP in colon cancer. However, the presence or absence of microsatellite instability has a major effect on the expression of this phenotype.
Genomic imprinting is a process that leads to the silencing of one allele of a gene in a parent of origin specific manner. Genes that are involved in this process are often regulated in clusters, one of which is the Peg3 (Paternally expressed gene 3) imprinted domain. We investigated this region for both CpG islands and long antisense transcripts, two common features of imprinted gene clusters. First, we performed a systematic survey of DNA methylation status of the CpG islands in this region of the mouse, cow, and human genomes. We identified two previously unreported differentially methylated regions (DMR): one in the promoter region of mouse Zim3 and another in the promoter region of human USP29. The PEG3-CpG island is the only DMR that is conserved among these three species. PEG3 has been implicated in several types of cancer, so we examined the methylation status of several CpG islands in this region using human tumor derived DNA. The CpG islands near PEG3 and USP29 both showed hypermethylation in
CpG dinucleotides are known to play a crucial role in regulatory domains, affecting gene expression in their natural context. Here, we demonstrate that intragenic CpG frequency and distribution impacts transgene and genomic gene expression levels in mammalian cells. As shown for the Macrophage Inflammatory Protein 1α, de novo RNA synthesis correlates with the number of CpG dinucleotides, whereas RNA splicing, stability, nuclear export and translation are not affected by the sequence modification. Differences in chromatin accessibility in vivo and altered nucleosome positioning in vitro suggest that increased CpG levels destabilize the chromatin structure. Moreover, enriched CpG levels correlate with increased RNA polymerase II elongation rates in vivo. Interestingly, elevated CpG levels particularly at the 5 end of the gene promote efficient transcription. We show that this is a genome-wide feature of highly expressed genes, by identifying a domain of ∼700 bp with high CpG content downstream of the
All the human tissue specimens used in this study were obtained as part of our ongoing work aimed at characterizing molecular alterations in endometrial cancer. All participants consented to molecular analyses and follow-up. These protocols have been approved by the Washington University Medical Centers Human Studies Committee.. Differential methylation hybridization analysis. Procedures used for tissue DNA extraction have been described previously (15). Differential methylation hybridization (DMH) analysis was done using high-density slide arrays containing 7,776 CpG island clones (MseI CpG inserts) using 20 endometrial cancer (endometrioid histology, ,70% neoplastic cellularity) and three pooled normal endometrium DNAs as a reference control. Tumor and control amplicons were labeled with Cy5 and Cy3, respectively, and cohybridized onto microarray slides using our established protocols (16). Normalized Cy5/Cy3 hybridization intensities were calculated, and candidate loci with ratios ,1.5 were ...
DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. The bulk of mammalian DNA has about 40% of CpG sites methylated but there are certain areas, know as CpG islands which are GC rich (made up of about 65% CG residues) where none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. 1-2% of the human genome are CpG clusters and there is an inverse relationship between CpG methylation and transcriptional activity.. ...
Purpose: To carry out the mutation analysis of the KIF21A gene in a four-generation Indian family affected with CFEOM1 and to find out the molecular basis of the most frequent mutations c.2860C,T and c.2861G,A in exon 21 of the KIF21A gene. Methods: Mutational analysis was carried out by direct automated sequencing of the PCR products from exons 8, 20, and 21 of the KIF21A gene. Allele specific oligo hybridization analysis was carried out to study the segregation of the mutation within the family. Methylation status of the mutated CpG dinucleotide in exon 21 was detected using bisulfite genomic sequencing technique on genomic DNA isolated from blood and sperms. Results: We found a previously reported missense mutation c.2860C,T (p.954R,W) in exon 21 of the KIF21A gene in our family. This mutation was found in a CpG dinucleotide. Bisulfite genomic sequencing revealed that all the CpG dinucleotides in exon 21 including the one which harbored the two most frequent mutations were methylated both in ...
Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is activated. We show that CpG DNA binds directly to TLR9 in ligand-binding studies. CpG DNA moves into early endosomes and is subsequently transported to a tubular lysosomal compartment. Concurrent with the movement of CpG DNA in cells, TLR9 redistributes from the ER to CpG DNA-containing structures, which also accumulate MyD88. Our data indicate a previously unknown mechanism of cellular activation involving the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where signal transduction is initiated.
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West DB, Engelhard EK, Adkisson M, Nava AJ, Kirov J, Cipollone A, Willis BJ, Rapp J, de Jong P, Lloyd KCK. Transcriptome analysis of targeted mouse mutations reveals the topography of local changes in gene expression. PLOS Genetics. 2016 Feb 3;12(2).. Lloyd KCK, Khanna C, Hendricks W, Trent J, and Kotlikoff M. Precision medicine: an opportunity for a paradigm shift in veterinary medicine. JAVMA. 2016;248:45-48.. Jong Pieter, West DB. Reporter gene silencing in targeted mouse mutants is associated with promoter CpG island methylation. PLoS One. 2015 Aug 14;10(8).. Karp NA, Meehan TF, Morgan H, Mason JC, Blake A, Kurbatova N, Smedley D, Jacobsen J, Mott JF, Iyer V, Matthews P, Melvin DG, Wells S, Flenniken AM, Masuya H, Wakana S, White JK, Lloyd KCK, Reynolds CL, Paylor R, West DB, Svenson KL, Chesler EJ, Hrab? de Angelis MH, Tocchini-Valentini GP, Sorg-Guss T, Herault Y, Parkinson H, Mallon A-M, Brown SD. Applying the ARRIVE guidelines to an in vivo database. PLoS Biol. 2015 May ...
Kaplan-Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan-M
Is designed to test for association between methylation at CpG sites across the genome and a phenotype of interest, adjusting for any relevant covariates. The package can perform standard analyses of large datasets very quickly with no need to impute the data. It can also handle mixed effects models with chip or batch entering the model as a random intercept. Also includes tools to apply quality control filters, perform permutation tests, and create QQ plots, manhattan plots, and scatterplots for individual CpG sites. ...
Identify and plot CpG islands in nucleotide sequence(s) Version: EMBOSS:6.5.0.0 Standard (Mandatory) qualifiers (* if not always prompted): [-sequence] seqall Nucleotide sequence(s) filename and optional format, or reference (input USA) -window integer [100] The percentage CG content and the Observed frequency of CG is calculated within a window whose size is set by this parameter. The window is moved down the sequence and these statistics are calculated at each position that the window is moved to. (Integer 1 or more) -minlen integer [200] This sets the minimum length that a CpG island has to be before it is reported. (Integer 1 or more) -minoe float [0.6] This sets the minimum average observed to expected ratio of C plus G to CpG in a set of 10 windows that are required before a CpG island is reported. (Number from 0.000 to 10.000) -minpc float [50.] This sets the minimum average percentage of G plus C a set of 10 windows that are required before a CpG island is reported. (Number from 0.000 to ...
Human miR-133a is encoded by 2 distinct genes, miR-133a-1 and miR-133a-2, which are processed into an identical mature sequence (http://www.mirbase.org). miR-133a-1 and miR-133a-2 are embedded in the MIB1 gene on chromosome 18 and C20orf166 on chromosome 20, respectively. The sequence of miR-133b differs from miR-133a with a single nucleotide on the 3′ flank. However, the Ct values of miR-133b in normal tissues were significantly lower than that of miR-133a (data not shown), suggesting that miR-133a is the dominant form of miR-133 in normal colorectal tissue. Epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is a common hallmark of human tumors (11). Most recently, it was documented that hypermethylation of the CpG islands upstream of miR-1-133a might be involved in the downregulation of miR-133a in CRCs (12). In the present study, we showed that miR-133a was significantly downregulated in primary CRC tissues using microdissection technique.. The ...
In mammalian genomes, many of the high CG-dinucleotide content regions occur in or near the promoters of genes. The so-called CpG islands are
TY - JOUR. T1 - Coadministration of antigen-conjugated and free CpG. T2 - Effects of in vitro and in vivo interactions in a murine model. AU - Herbáth, Melinda. AU - Szekeres, Zsuzsanna. AU - Kövesdi, Dorottya. AU - Papp, Krisztián. AU - Erdei, Anna. AU - Prechl, József. PY - 2014/8. Y1 - 2014/8. N2 - CpG oligodeoxynucleotides (CpG) are widely studied as promising adjuvants in vaccines against a range of diseases including infection, cancer or allergy. Conjugating antigen to CpG has been shown to potentiate the adjuvant effect via enhancing antigen uptake and danger signaling by the very same cell. In the present study, using biotinylated CpG and streptavidin as a model system, we demonstrate that CpG motif containing free and antigen-conjugated oligonucleotides do not compete in terms of cell activation via TLR9, but do compete for cellular uptake. Antigen-conjugated CpG enhances cellular association and uptake of the antigen by antigen-presenting cells (APC) and T cells. Free CpG ...
We sequenced the CpG island within exon 1 of the TCF21 gene from 10 lung cancer cell lines and 2 HBECs (18) and also analyzed them for gene expression. The results showed that all the 19 CpG sites were methylated in 9 of 10 lung cancer cell lines, whereas 8 specific CpG sites of the 19 were unmethylated only in H661 (a cancer cell line) and in the HBECs (Fig. 1). All methylation-positive cancer cell lines were negative for TCF21 expression (relative expression ,0.50). H661 and HBECs were negative for methylation and positive for TCF21 expression (relative expression ≥1; Fig. 1). 5-Aza-2′-deoxycytidine treatment to four lung cell lines (H1299, H2887, HCC95, and H661) resulted into reactivation of TCF21 expression in all the cell lines, except H661, which was positive for TCF21 expression in untreated population (data not shown). The results suggest that methylation of the specific sites is related to gene silencing. However, it is possible that other factors in addition to methylation (19) ...
In this work, we establish basic molecular-level understanding of the ways by which patterns of CpG dinucleotides evolve in mammalian genomes. According to the results, the evolution of CpG distributions is driven by a complex combination of a context-dependent mutational process, variation in germ-line methylation levels, and selection against loss of functional CpGs. The context-dependent mutational process renders CpGs in mutation-favoring sequence contexts up to 40 times more mutable than CpGs in mutation-resistant contexts. Changes in germ-line methylation levels may be responsible for much of this variability by increasing the rate of 5-methylcytosine deamination in highly methylated regions. Selection on functional CpGs also plays a major role and is likely to constrain a substantial subset of the genomic CpGs (SI Fig. 10). All three factors are together shaping a challenging evolutionary landscape, contributing to the still-elusive functional role of DNA methylation in central processes ...
RESULTS: Cultures derived from irradiated cells contained significantly more vHMEC, lacking senescence associated beta-galactosidase or p16 expression, than cultures derived from unirradiated cells. As expected, post-stasis vHMEC cultures derived from both unirradiated and irradiated cells exhibited more extensive methylation of the p16 gene than pre-stasis HMEC cultures. However, the extent of methylation of individual CpG sites in vHMEC samples did not correlate with passage number or treatment. Exposure to sparsely or densely ionizing radiation elicited similar increases in the numbers of vHMEC compared to unirradiated controls. Agent-based modeling indicated that radiation-induced premature senescence of normal HMEC most likely accelerated vHMEC outgrowth through alleviation of spatial constraints. Subsequent experiments using defined co-cultures of vHMEC and senescent cells supported this mechanism ...
Colorectal cancer (CRC) has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when -among other things- three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC ...
Distribution of differentially methylated CpG sites.(a) Overlap of hypermethylated and hypomethylated CpG sites in the expanded cell fractions. (b) For the gene
Publication date: Feb 28, 2020 CpG dinucleotides are suppressed in the genomes of many vertebrate RNA viruses, including HIV-1. The cellular antiviral protein ZAP (zinc finger antiviral protein) binds CpGs ... Read more ...
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The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Review of the effect of CpG dinucleotide on the immune response and the gene silencing of gene delivery vectors for gene therapy applications. Bacterial DNA is rich in unmethylated 2-deoxyribo (cytidine-phosphateguanosine) (CpG) dinucleotides, in contrast to mammalian DNA which contains a low frequency of CpG dinucleotides that are mostly methylated. Unmethylated CpGs in specific sequence contexts activate the vertebrate immune system. Genes with these sequences are recognized as foreign DNA by the vertebrate host leading to a progressive decline of their expression.
CpG ODNs are widely used for activation of immune cells or induction of signalling in TLR9-expressing recombinant cell lines. Control compounds which contain GpC dinucleotides instead of CpGs are useful to control for the CpG specificity of this effects. - USA
Ur results indicated that the statistical significance of most CpG units showed no obvious difference after the correction except for unit 2 and unit 36 in LEP
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TY - JOUR. T1 - Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia. AU - Pei, Lirong. AU - Choi, Jeong-Hyeon. AU - Liu, Jimei. AU - Lee, Eun Joon. AU - McCarthy, Brian. AU - Wilson, James M.. AU - Speir, Ethan. AU - Awan, Farrukh. AU - Tae, Hongseok. AU - Arthur, Gerald. AU - Schnabel, Jennifer L.. AU - Taylor, Kristen H.. AU - Wang, Xinguo. AU - Xu, Dong. AU - Ding, Hanfei. AU - Munn, David H. AU - Caldwell, Charles W.. AU - Shi, Huidong. PY - 2012/6. Y1 - 2012/6. N2 - We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1,764 gene promoters were identified as being ...