1008:
1166:(TEs) where TEs are not only responsible in the genome expansion but also CpG loss in a host DNA. TEs can be known as "methylation centers" whereby the methylation process, the TEs spreads into the flanking DNA once in the host DNA. This spreading might subsequently result in CpG loss over evolutionary time. Older evolutionary times show a higher CpG loss in the flanking DNA, compared to the younger evolutionary times. Therefore, the DNA methylation can lead eventually to the noticeably loss of CpG sites in neighboring DNA.
578:, or TDG) that specifically replaces T's from T/G mismatches. However, due to the rarity of CpGs, it is theorised to be insufficiently effective in preventing a possibly rapid mutation of the dinucleotides. The existence of CpG islands is usually explained by the existence of selective forces for relatively high CpG content, or low levels of methylation in that genomic area, perhaps having to do with the regulation of gene expression. A 2011 study showed that most CpG islands are a result of non-selective forces.
1047:
675:
protein coding genes, suggesting that about 867 genes in a colon tumor have lost expression due to CpG island methylation. A separate study found an average of 1,549 differentially methylated regions (hypermethylated or hypomethylated) in the genomes of six colon cancers (compared to adjacent mucosa), of which 629 were in known promoter regions of genes. A third study found more than 2,000 genes differentially methylated between colon cancers and adjacent mucosa. Using
330:
587:
566:, in vertebrates. A C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the cytosines 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 time methylated cytosines tend to turn into
4246:
1175:
38:
290:
283:
1193:
the insertion into a host DNA can produce DNA methylation and provoke a spreading into the
Flanking DNA area. This spreading is why there are is considerable CpG loss and genome expansion. However, this is a result that is analyzed over time because older Alus elements show more CpG loss in sites of neighboring DNA compared to younger ones.
535:. Based on an extensive search on the complete sequences of human chromosomes 21 and 22, DNA regions greater than 500 bp were found more likely to be the "true" CpG islands associated with the 5' regions of genes if they had a GC content greater than 55%, and an observed-to-expected CpG ratio of 65%.
1178:
CpG methylation contributes to the genome expansion and consequently to CpG depletion. This picture shows a genome with no TEs and unmethylated CpG sites, and the insertion and transposition of a TE lead to methylation and silencing of the TE. Through the process of CpG methylation a decrease in CpG
994:
neurons were differentially methylated. However while the hippocampus is essential for learning new information it does not store information itself. In the mouse experiments of Halder, 1,206 differentially methylated genes were seen in the hippocampus one hour after contextual fear conditioning but
320:
et al. since the Venter et al. genome sequence did not include the interiors of highly similar repetitive elements and the extremely dense repeat regions near the centromeres. Since CpG islands contain multiple CpG dinucleotide sequences, there appear to be more than 20 million CpG dinucleotides in
1192:
Alu elements are known as the most abundant type of transposable elements. Some studies have used Alu elements as a way to study the factors responsible for genome expansion. Alu elements are CpG-rich in a longer amount of sequence, unlike LINEs and ERVs. Alus can work as a methylation center, and
686:
One 2012 study listed 147 specific genes with colon cancer-associated hypermethylated promoters, along with the frequency with which these hypermethylations were found in colon cancers. At least 10 of those genes had hypermethylated promoters in nearly 100% of colon cancers. They also indicated 11
674:
or passenger mutations. In contrast, in one study of colon tumors compared to adjacent normal-appearing colonic mucosa, 1,734 CpG islands were heavily methylated in tumors whereas these CpG islands were not methylated in the adjacent mucosa. Half of the CpG islands were in promoters of annotated
657:. The presence of multiple methylated CpG sites in CpG islands of promoters causes stable silencing of genes. Silencing of a gene may be initiated by other mechanisms, but this is often followed by methylation of CpG sites in the promoter CpG island to cause the stable silencing of the gene.
1183:
There is generally an inverse correlation between genome size and number of CpG islands, as larger genomes typically have a greater number of transposable elements. Selective pressure against TE's is substantially reduced if expression is suppressed via methylation, further TE's can act as
1184:"methylation centres" facilitating methylation of flanking DNA. Since methylation reduces selective pressure on nucleotide sequence long term methylation of CpG sites increases accumulation of spontaneous cytosine to thymine transitions, thereby resulting in a loss of Cp sites.
959:
to DNA bases) exhibit a sequence preference for cytosines within CpG sites. In the mouse brain, 4.2% of all cytosines are methylated, primarily in the context of CpG sites, forming 5mCpG. Most hypermethylated 5mCpG sites increase the repression of associated genes.
315:
CpG dinucleotides frequently occur in CpG islands (see definition of CpG islands, below). There are 28,890 CpG islands in the human genome, (50,267 if one includes CpG islands in repeat sequences). This is in agreement with the 28,519 CpG islands found by
333:
How methylation of CpG sites followed by spontaneous deamination leads to a lack of CpG sites in methylated DNA. As a result, residual CpG islands are created in areas where methylation is rare, and CpG sites stick (or where C to T mutation is highly
45:, the " 5'βCβphosphateβGβ3' " sequence of nucleotides, is indicated on one DNA strand (in yellow). On the reverse DNA strand (in blue), the complementary 5'βCpGβ3' site is shown. A C-G base-pairing between the two DNA strands is also indicated (right)
508:
695:
to direct post-transcriptional repression. On average, each microRNA represses several hundred target genes. Thus microRNAs with hypermethylated promoters may be allowing over-expression of hundreds to thousands of genes in a cancer.
435:
995:
these altered methylations were reversed and not seen after four weeks. In contrast with the absence of long-term CpG methylation changes in the hippocampus, substantial differential CpG methylation could be detected in
2807:"Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix"
111:. In mammals, 70% to 80% of CpG cytosines are methylated. 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
538:
CpG islands are characterized by CpG dinucleotide content of at least 60% of that which would be statistically expected (~4β6%), whereas the rest of the genome has much lower CpG frequency (~1%), a phenomenon called
189:
CpG dinucleotides have long been observed to occur with a much lower frequency in the sequence of vertebrate genomes than would be expected due to random chance. For example, in the human genome, which has a 42%
699:
The information above shows that, in cancers, promoter CpG hyper/hypo-methylation of genes and of microRNAs causes loss of expression (or sometimes increased expression) of far more genes than does mutation.
665:
In cancers, loss of expression of genes occurs about 10 times more frequently by hypermethylation of promoter CpG islands than by mutations. For example, in a colorectal cancer there are usually about 3 to 6
559:. Most of the methylation differences between tissues, or between normal and cancer samples, occur a short distance from the CpG islands (at "CpG island shores") rather than in the islands themselves.
777:. About seventeen types of cancer are frequently deficient in one or more DNA repair genes due to hypermethylation of their promoters. As an example, promoter hypermethylation of the DNA repair gene
990:) and the expression of 564 genes was up-regulated (often associated with hypomethylation of CpG sites in gene promoters). At 24 hours after training, 9.2% of the genes in the rat genome of
1151:, allowing TET1 to oxidize the 5mC adjacent to 8-OHdG, as shown in the first figure in this section. This initiates the demethylation pathway shown in the second figure in this section.
383:
345:, a GC percentage greater than 50%, and an observed-to-expected CpG ratio greater than 60%. The "observed-to-expected CpG ratio" can be derived where the observed is calculated as:
231:
341:(or CG islands) are regions with a high frequency of CpG sites. Though objective definitions for CpG islands are limited, the usual formal definition is a region with at least 200
3038:
Newman RE, Soldatenkov VA, Dritschilo A, Notario V (2002). "Poly(ADP-ribose) polymerase turnover alterations do not contribute to PARP overexpression in Ewing's sarcoma cells".
691:
whose promoters were hypermethylated in colon cancers at frequencies between 50% and 100% of cancers. MicroRNAs (miRNAs) are small endogenous RNAs that pair with sequences in
999:
neurons during memory maintenance. There were 1,223 differentially methylated genes in the anterior cingulate cortex of mice four weeks after contextual fear conditioning.
871:
DNA damage appears to be the primary underlying cause of cancer. If accurate DNA repair is deficient, DNA damages tend to accumulate. Such excess DNA damage can increase
528:
have their promoters embedded in CpG islands. Given the frequency of GC two-nucleotide sequences, the number of CpG dinucleotides is much lower than would be expected.
3853:
Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, Pan F, Zhao J, Hu Z, Sekhar C, Guo Z (September 2016). "OGG1 is essential in oxidative stress induced DNA demethylation".
963:
As reviewed by Duke et al., neuron DNA methylation (repressing expression of particular genes) is altered by neuronal activity. Neuron DNA methylation is required for
783:
occurs in 93% of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40%-90% of colorectal cancers and 50% of brain cancers. Promoter hypermethylation of
683:
were hypermethylated and 369 were hypomethylated in cancers. Hypomethylation of CpG islands in promoters results in overexpression of the genes or gene sets affected.
547:
of a gene, in most instances the CpG sites in the CpG islands of promoters are unmethylated if the genes are expressed. This observation led to the speculation that
440:
1086:). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex
1154:
Altered protein expression in neurons, controlled by ROS-dependent demethylation of CpG sites in gene promoters within neuron DNA, is central to memory formation.
2141:
388:
1383:; Linton, Lauren M.; Birren, Bruce; Nusbaum, Chad; Zody, Michael C.; Baldwin, Jennifer; Devon, Keri; Dewar, Ken; Doyle, Michael (15 February 2001).
3175:"Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells"
779:
2907:"c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase-Activated Leukemias"
864:
is over-expressed in tyrosine kinase-activated leukemias, in neuroblastoma, in testicular and other germ cell tumors, and in Ewing's sarcoma,
3434:
2871:
2410:
2117:
2038:
1135:
is a key enzyme involved in demethylating 5mCpG. However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form
1125:
of thousands of CpG sites during memory formation depends on initiation by ROS. In 2016, Zhou et al., showed that ROS have a central role in
248:, and the resulting G:T mismatched bases are often improperly resolved to A:T; whereas the deamination of unmethylated cytosine results in a
857:
170:
81:
4158:
1597:
520:
In mammalian genomes, CpG islands are typically 300β3,000 base pairs in length, and have been found in or near approximately 40% of
298:
3452:"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island"
3425:
Bernstein, C; Prasad, AR; Nfonsam, V; Bernstein, H. (2013). "Chapter 16: DNA Damage, DNA Repair and Cancer". In Chen, Clark (ed.).
2056:"Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level"
1074:(5hmC). In successive steps TET enzymes further hydroxylate 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC).
2995:
Mego M, Cierna Z, Svetlovska D, Macak D, Machalekova K, Miskovska V, et al. (2013). "PARP expression in germ cell tumours".
1148:
1132:
1067:
1063:
1059:
1040:
3216:"Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis"
967:; is modified by experiences; and active DNA methylation and demethylation is required for memory formation and maintenance.
895:). Thus, CpG island hyper/hypo-methylation in the promoters of DNA repair genes are likely central to progression to cancer.
653:
In humans, DNA methylation occurs at the 5 position of the pyrimidine ring of the cytosine residues within CpG sites to form
169:
of cytosine and guanine for double-stranded sequences. The CpG notation is therefore to be interpreted as the cytosine being
903:
Since age has a strong effect on DNA methylation levels on tens of thousands of CpG sites, one can define a highly accurate
2254:"The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores"
1523:"Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution"
1139:(8-OHdG), resulting in a 5mCp-8-OHdG dinucleotide (see first figure in this section). After formation of 5mCp-8-OHdG, the
820:
810:
805:
800:
708:
DNA repair genes are frequently repressed in cancers due to hypermethylation of CpG islands within their promoters. In
4266:
2393:
Kaur S, Lotsari-Salomaa JE, SeppΓ€nen-Kaijansinkko R, PeltomΓ€ki P (2016). "MicroRNA Methylation in
Colorectal Cancer".
2249:
1007:
928:
667:
181:, the latter meaning that a guanine is followed by a cytosine in the 5' β 3' direction of a single-stranded sequence.
1058:
As reviewed in 2018, in brain neurons, 5mC is oxidized by the ten-eleven translocation (TET) family of dioxygenases (
868:
is over-expressed in the majority of cancers of the breast, prostate, stomach, neuroblastomas, pancreatic, and lung.
233:
of the time. The frequency of CpG dinucleotides in human genomes is less than one-fifth of the expected frequency.
4236:
1136:
1028:
1964:"A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters"
1267:"A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters"
996:
1039:
targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits
3256:
3130:(2006). "Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score".
2544:
Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R,
1208:
912:
904:
610:
348:
127:
28:
3552:
Field, Adam E.; Robertson, Neil A.; Wang, Tina; Havas, Aaron; Ideker, Trey; Adams, Peter D. (September 2018).
309:
of the APRT gene are indicated (blue), and the start (ATG) and stop (TGA) codons are emphasized (bold blue).
1114:
1075:
1071:
630:
575:
517:). Because of this, the presence of a CpG island is used to help in the prediction and annotation of genes.
201:
2107:
531:
A 2002 study revised the rules of CpG island prediction to exclude other GC-rich genomic sequences such as
3595:"Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA"
1147:
binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to the 5mCp-8-OHdG site recruits
1144:
1036:
970:
In 2016 Halder et al. using mice, and in 2017 Duke et al. using rats, subjected the rodents to contextual
4152:
3386:"DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture"
952:
887:
alterations due to errors during DNA repair. Such mutations and epigenetic alterations can give rise to
257:
108:
2305:"Primate CpG Islands Are Maintained by Heterogeneous Evolutionary Regimes Involving Minimal Selection"
1046:
4185:
4104:
2497:
2168:
1975:
1876:
1816:
1750:
1534:
1463:
1396:
1278:
1163:
1140:
1032:
830:
796:
709:
253:
3354:
Nikolova T, Christmann M, Kaina B (2009). "FEN1 is overexpressed in testis, lung and brain tumors".
3307:"Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays"
1094:(Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 (
3890:"The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders"
2805:
Rieke DT, Ochsenreither S, Klinghammer K, Seiwert TY, Klauschen F, Tinhofer I, et al. (2016).
1518:
987:
964:
936:
680:
676:
671:
606:
514:
123:
1027:-pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming
3287:
3155:
3020:
2334:
2135:
1615:
1227:
Jabbari K, Bernardi G (May 2004). "Cytosine methylation and CpG, TpG (CpA) and TpA frequencies".
556:
521:
3644:"Genomic distribution and inter-sample variation of non-CpG methylation across human cell types"
2905:
Muvarak N, Kelley S, Robert C, Baer MR, Perrotti D, Gambacorti-Passerini C, et al. (2015).
1106:). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield
982:
brain region of rats, the expression of 1,048 genes was down-regulated (usually associated with
3801:"DNA methylation changes in plasticity genes accompany the formation and maintenance of memory"
3593:
Ramirez-Ortiz ZG, Specht CA, Wang JP, Lee CK, Bartholomeu DC, Gazzinelli RT, Levitz SM (2008).
503:{\displaystyle (({\text{number of }}C+{\text{number of }}G)/2)^{2}/{\text{length of sequence}}}
4221:
4203:
4140:
4122:
4068:
4019:
3990:"Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity"
3970:
3921:
3870:
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3781:
3729:
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3624:
3534:
3483:
3430:
3407:
3381:
3363:
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3279:
3237:
3196:
3147:
3104:
3055:
3012:
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2836:
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2632:
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2523:
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2003:
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1122:
1012:
971:
563:
525:
2214:
Feil R, Berger F (2007). "Convergent evolution of genomic imprinting in plants and mammals".
1019:
In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides (
629:, where the CpG island-containing element is located about 5,400 nucleotides upstream of the
4211:
4193:
4130:
4112:
4058:
4050:
4009:
4001:
3960:
3952:
3911:
3901:
3862:
3820:
3812:
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Halder R, Hennion M, Vidal RO, Shomroni O, Rahman RU, Rajput A, et al. (January 2016).
3771:
3763:
3719:
3709:
3665:
3655:
3614:
3606:
3573:
3565:
3524:
3514:
3473:
3463:
3397:
3326:
3318:
3305:
Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. (2003).
3271:
3227:
3186:
3139:
3094:
3086:
3075:"Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers"
3047:
3004:
2967:
2926:
2918:
2877:
2859:
2826:
2818:
2777:
2769:
2720:
2712:
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2612:
2571:
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2513:
2505:
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2316:
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2223:
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1993:
1983:
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1404:
1352:
1344:
1296:
1286:
1236:
1051:
1024:
908:
754:
726:
654:
551:
of CpG sites in the promoter of a gene may inhibit gene expression. Methylation, along with
96:
562:
CpG islands typically occur at or near the transcription start site of genes, particularly
3127:
2650:
Beggs AD, Jones A, El-Bahrawy M, El-Bahwary M, Abulafi M, Hodgson SV, et al. (2013).
2481:
2354:"Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas"
2258:
1627:
1079:
876:
746:
620:
595:
329:
92:
4189:
4108:
3255:
Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, et al. (2005).
2956:"Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma"
2501:
2172:
1979:
1880:
1820:
1754:
1711:
1694:
1538:
1467:
1400:
1282:
1113:
Two reviews summarize the large body of evidence for the critical and essential role of
712:
at least 15 DNA repair genes have frequently hypermethylated promoters; these genes are
513:
Many genes in mammalian genomes have CpG islands associated with the start of the gene (
4250:
4216:
4173:
4135:
4092:
4063:
4038:
4014:
3989:
3965:
3940:
3916:
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2253:
2080:
2055:
1998:
1963:
1670:
1645:
1641:
1357:
1332:
1301:
1266:
1043:
and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC.
860:. If this pathway is over-expressed the excess mutations it causes can lead to cancer.
540:
430:{\displaystyle ({\text{number of }}C*{\text{number of }}G)/{\text{length of sequence}}}
3322:
3257:"Genome-wide analysis of gene expression in neuroblastomas detected by mass screening"
2191:
2156:
2030:
2023:
1899:
1864:
1557:
1522:
297:
Distribution of CpG sites (left: in red) and GpC sites (right: in green) in the human
4260:
3143:
3123:
2854:
Jin B, Robertson KD (2013). "DNA Methyltransferases, DNA Damage Repair, and Cancer".
2103:
2054:
Fatemi M, Pao MM, Jeong S, Gal-Yam EN, Egger G, Weisenberger DJ, et al. (2005).
1935:
1695:"Understanding what determines the frequency and pattern of human germline mutations"
1646:"Understanding what determines the frequency and pattern of human germline mutations"
692:
638:
544:
237:
4172:
Zhou, Wanding; Liang, Gangning; Molloy, Peter L.; Jones, Peter A. (11 August 2020).
4091:
Zhou, Wanding; Liang, Gangning; Molloy, Peter L.; Jones, Peter A. (11 August 2020).
3291:
3159:
2338:
586:
4271:
2753:
1860:
1852:
1800:
1796:
1737:, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. (February 2001).
956:
590:
An image showing a hypothetical evolutionary mechanism behind CpG island formation.
532:
317:
104:
73:
3866:
3402:
3385:
3090:
3073:
Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, Kernstine KH, Lin D, Shen B (2008).
3024:
3008:
2972:
2955:
2922:
2550:"Orphan CpG islands identify numerous conserved promoters in the mammalian genome"
1584:. Current Topics in Microbiology and Immunology. Vol. 301. pp. 283β315.
301:
gene. CpG are more abundant in the upstream region of the gene, where they form a
3660:
3642:
Ziller MJ, MΓΌller F, Liao J, Zhang Y, Gu H, Bock C, et al. (December 2011).
3569:
3519:
3468:
3275:
2566:
2397:. Advances in Experimental Medicine and Biology. Vol. 937. pp. 109β22.
17:
2863:
2545:
2437:
2402:
1734:
1380:
1328:
991:
979:
884:
623:
elements also frequently contain CpG islands. An example is the DNA repair gene
571:
548:
241:
112:
4245:
4178:
Proceedings of the
National Academy of Sciences of the United States of America
4097:
Proceedings of the
National Academy of Sciences of the United States of America
3191:
3174:
2858:. Advances in Experimental Medicine and Biology. Vol. 754. pp. 3β29.
2321:
2304:
1240:
1174:
848:, were hypomethylated and these genes were over-expressed in numerous cancers.
2822:
2716:
2652:"Whole-genome methylation analysis of benign and malignant colorectal tumours"
2227:
880:
302:
195:
191:
162:
notation is used to distinguish this single-stranded linear sequence from the
155:
65:
4207:
4126:
3941:"Reactive oxygen species in the regulation of synaptic plasticity and memory"
3906:
2127:
1589:
1495:
1428:
923:
Unmethylated CpG dinucleotide sites can be detected by Toll-like receptor 9 (
4198:
4117:
2509:
1988:
1829:
1804:
1547:
1291:
1020:
342:
260:
rate at methylated CpG sites is ~10 fold higher than at unmethylated sites.
166:
151:
77:
4225:
4144:
4072:
4023:
3974:
3925:
3874:
3834:
3785:
3733:
3679:
3628:
3538:
3487:
3411:
3367:
3340:
3283:
3241:
3232:
3215:
3200:
3151:
3108:
3059:
3016:
2981:
2940:
2891:
2840:
2791:
2734:
2685:
2636:
2617:
2601:"Discovery and Validation of Hypermethylated Markers for Colorectal Cancer"
2585:
2527:
2467:
2420:
2379:
2330:
2289:
2235:
2200:
2181:
2089:
2007:
1908:
1889:
1838:
1782:
1720:
1679:
1607:
1566:
1503:
1436:
1366:
1310:
1248:
1090:
deaminases to form 5-hydroxymethyluracil (5hmU) or 5mC can be converted to
37:
3956:
3767:
2773:
1943:
1922:
Gardiner-Garden M, Frommer M (1987). "CpG islands in vertebrate genomes".
3714:
3610:
2071:
1773:
1486:
1419:
1107:
1087:
932:
892:
872:
688:
642:
62:
2252:, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, et al. (2009).
1348:
856:
are essential genes in the error-prone and mutagenic DNA repair pathway
4005:
3554:"DNA Methylation Clocks in Aging: Categories, Causes, and Consequences"
3051:
2458:
2441:
1091:
1083:
567:
552:
245:
116:
69:
4174:"DNA methylation enables transposable element-driven genome expansion"
4093:"DNA methylation enables transposable element-driven genome expansion"
3173:
Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, et al. (2005).
2667:
2370:
2353:
2157:"Comprehensive analysis of CpG islands in human chromosomes 21 and 22"
198:
consisting of cytosine followed by guanine would be expected to occur
2484:, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (2013).
1763:
1738:
1476:
1451:
1409:
1384:
1162:
CpG depletion has been observed in the process of DNA methylation of
1118:
1078:(TDG) recognizes the intermediate bases 5fC and 5caC and excises the
983:
975:
940:
888:
762:
734:
249:
100:
4054:
3816:
3698:"The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function"
2954:
Newman EA, Lu F, Bashllari D, Wang L, Opipari AW, Castle VP (2015).
1661:
289:
282:
34:
Region of often-methylated DNA with a cytosine followed by a guanine
3752:"Experience-dependent epigenomic reorganization in the hippocampus"
2271:
2029:(6th ed.). Mississauga: Jones & Bartlett, Canada. p.
252:, which as a foreign base is quickly replaced by a cytosine by the
1173:
1099:
1095:
924:
861:
838:
825:
791:
789:
occurs in 82% of colorectal cancers. Promoter hypermethylation of
758:
750:
742:
738:
730:
714:
625:
328:
2701:"Epigenetics Offer New Horizons for Colorectal Cancer Prevention"
943:
in humans. This is used to detect intracellular viral infection.
1202:
1103:
1031:(8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The
865:
844:
815:
785:
773:
766:
722:
718:
704:
DNA repair genes with hyper/hypo-methylated promoters in cancers
306:
84:. CpG sites occur with high frequency in genomic regions called
1580:
Walsh CP, Xu GL (2006). "Cytosine
Methylation and DNA Repair".
1450:
International Human Genome
Sequencing Consortium (2001-02-15).
3750:
Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD (July 2017).
3501:
Cuozzo C, Porcellini A, Angrisano T, et al. (July 2007).
58:
3122:
Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, Zeng G,
3503:"DNA damage, homology-directed repair, and DNA methylation"
1803:, Li PW, Mural RJ, Sutton GG, et al. (February 2001).
524:
of mammalian genes. Over 60% of human genes and almost all
3988:
Beckhauser TF, Francis-Oliveira J, De
Pasquale R (2016).
2758:"Most mammalian mRNAs are conserved targets of microRNAs"
637:
gene. CpG islands also occur frequently in promoters for
823:
squamous cell carcinomas. Promoter hypermethylation of
236:
This underrepresentation is a consequence of the high
150:, that is, cytosine and guanine separated by only one
4234:
1739:"Initial sequencing and analysis of the human genome"
1452:"Initial sequencing and analysis of the human genome"
1385:"Initial sequencing and analysis of the human genome"
443:
391:
351:
240:
of methylated CpG sites: the spontaneously occurring
204:
130:
of a gene (proximal promoters) contain a CpG island.
2352:
Chen HY, Shao CJ, Chen FR, Kwan AL, Chen ZP (2010).
1865:"On the sequencing and assembly of the human genome"
978:
to form. At 24 hours after the conditioning, in the
2599:Wei J, Li G, Dang S, Zhou Y, Zeng K, Liu M (2016).
1170:
Genome size and CpG ratio are negatively correlated
2022:
502:
429:
377:
225:
1333:"CpG islands and the regulation of transcription"
305:, whereas GpC are more evenly distributed. The 5
185:Under-representation caused by high mutation rate
2442:"DNA methylation patterns and epigenetic memory"
1003:Demethylation at CpG sites requires ROS activity
649:Methylation of CpG islands stably silences genes
3745:
3743:
836:On the other hand, the promoters of two genes,
2539:
2537:
1957:
1955:
1953:
1322:
1320:
1260:
1258:
2112:(Sixth ed.). New York, NY. p. 406.
661:Promoter CpG hyper/hypo-methylation in cancer
8:
3691:
3689:
3450:O'Hagan HM, Mohammad HP, Baylin SB (2008).
2140:: CS1 maint: location missing publisher (
1693:SΓ©gurel L, Wyman MJ, Przeworski M (2014).
267:
4215:
4197:
4134:
4116:
4062:
4013:
3964:
3915:
3905:
3824:
3775:
3723:
3713:
3669:
3659:
3618:
3577:
3528:
3518:
3477:
3467:
3401:
3330:
3231:
3190:
3098:
2971:
2930:
2881:
2830:
2781:
2724:
2675:
2626:
2616:
2575:
2565:
2517:
2457:
2369:
2320:
2279:
2190:
2180:
2079:
1997:
1987:
1898:
1888:
1828:
1772:
1762:
1710:
1669:
1556:
1546:
1485:
1475:
1418:
1408:
1356:
1300:
1290:
613:of a gene (proximal promoters) contain a
582:Methylation, silencing, cancer, and aging
495:
490:
484:
472:
461:
450:
442:
422:
417:
406:
395:
390:
378:{\displaystyle ({\text{number of }}CpGs)}
355:
350:
203:
1045:
1006:
585:
36:
4241:
3848:
3846:
3844:
2432:
2430:
2303:Cohen N, Kenigsberg E, Tanay A (2011).
2025:Genetics: Analysis of Genes and Genomes
1219:
574:. There is a special enzyme in humans (
115:. Methylated cytosines often mutate to
4150:
4039:"DNA methylation and memory formation"
3429:. BoD β Books on Demand. p. 413.
2699:Schnekenburger M, Diederich M (2012).
2133:
1962:Saxonov S, Berg P, Brutlag DL (2006).
1623:
1613:
1265:Saxonov S, Berg P, Brutlag DL (2006).
883:. Excess DNA damage can also increase
710:head and neck squamous cell carcinomas
244:of a methylated cytosine results in a
226:{\displaystyle 0.21\times 0.21=4.41\%}
91:Cytosines in CpG dinucleotides can be
4086:
4084:
4082:
3427:New Research Directions in DNA Repair
2856:Epigenetic Alterations in Oncogenesis
1188:Alu elements as promoters of CpG loss
7:
2395:Non-coding RNAs in Colorectal Cancer
1205:, detector of unmethylated CpG sites
1102:), or methyl-CpG binding protein 4 (
4037:Day JJ, Sweatt JD (November 2010).
1712:10.1146/annurev-genom-031714-125740
1082:resulting in an apyrimidinic site (
1805:"The sequence of the human genome"
858:microhomology-mediated end joining
220:
25:
1582:DNA Methylation: Basic Mechanisms
899:Methylation of CpG sites with age
4244:
3939:Massaad CA, Klann E (May 2011).
3144:10.1111/j.1464-410X.2006.06224.x
614:
288:
281:
85:
3888:Bayraktar G, Kreutz MR (2018).
3696:Fasolino M, Zhou Z (May 2017).
1098:), Nei-Like DNA Glycosylase 1 (
974:, causing an especially strong
813:. Promoter hypermethylation of
803:. Promoter hypermethylation of
154:group; phosphate links any two
3214:Wang K, Xie C, Chen D (2014).
481:
469:
447:
444:
414:
392:
372:
352:
1:
4157:: CS1 maint: date and year (
3867:10.1016/j.cellsig.2016.05.021
3403:10.1158/1541-7786.MCR-08-0020
3323:10.1016/S0002-9440(10)63911-9
3091:10.1158/1541-7786.MCR-08-0269
3009:10.1136/jclinpath-2012-201088
2973:10.1158/1541-7786.MCR-14-0337
2923:10.1158/1541-7786.MCR-14-0422
2109:Molecular biology of the cell
915:) in humans and chimpanzees.
3661:10.1371/journal.pgen.1002389
3570:10.1016/j.molcel.2018.08.008
3520:10.1371/journal.pgen.0030110
3469:10.1371/journal.pgen.1000155
3276:10.1016/j.canlet.2004.10.035
2567:10.1371/journal.pgen.1001134
1936:10.1016/0022-2836(87)90689-9
1924:Journal of Molecular Biology
1869:Proc. Natl. Acad. Sci. U.S.A
1271:Proc. Natl. Acad. Sci. U.S.A
929:plasmacytoid dendritic cells
555:modification, is central to
177:should not be confused with
2864:10.1007/978-1-4419-9967-2_1
2403:10.1007/978-3-319-42059-2_6
2021:Hartl DL, Jones EW (2005).
1137:8-hydroxy-2'-deoxyguanosine
1029:8-hydroxy-2'-deoxyguanosine
947:Role of CpG sites in memory
811:non-small-cell lung cancers
801:non-small-cell lung cancers
4288:
3192:10.1158/1078-0432.473.11.2
2705:Curr Colorectal Cancer Rep
2486:"Cancer genome landscapes"
2322:10.1016/j.cell.2011.04.024
2155:Takai D, Jones PA (2002).
1241:10.1016/j.gene.2004.02.043
821:non-small-cell lung cancer
593:
543:. Unlike CpG sites in the
26:
2823:10.18632/oncotarget.12211
2717:10.1007/s11888-011-0116-z
2228:10.1016/j.tig.2007.02.004
937:natural killer (NK) cells
679:analysis, 569 out of 938
639:functional noncoding RNAs
296:
275:
272:
72:nucleotide in the linear
3907:10.3389/fnmol.2018.00169
1699:Annu Rev Genom Hum Genet
1590:10.1007/3-540-31390-7_11
1527:Proc Natl Acad Sci U S A
631:transcription start site
611:transcription start site
605:In humans, about 70% of
601:CpG islands in promoters
128:transcription start site
122:In humans, about 70% of
29:CpG oligodeoxynucleotide
27:Not to be confused with
4199:10.1073/pnas.1921719117
4118:10.1073/pnas.1921719117
2510:10.1126/science.1235122
1989:10.1073/pnas.0510310103
1830:10.1126/science.1058040
1548:10.1073/pnas.0404142101
1292:10.1073/pnas.0510310103
1076:Thymine-DNA glycosylase
1072:5-hydroxymethylcytosine
670:mutations and 33 to 66
576:Thymine-DNA glycosylase
570:because of spontaneous
3945:Antioxid. Redox Signal
3233:10.3892/ijmm.2014.1682
2748:Friedman RC, Farh KK,
2182:10.1073/pnas.052410099
2161:Proc Natl Acad Sci USA
1968:Proc Natl Acad Sci USA
1890:10.1073/pnas.092136699
1644:, Calabrese P (2009).
1180:
1055:
1016:
953:DNA methyltransferases
591:
504:
431:
379:
335:
256:mechanism. The C to T
227:
109:DNA methyltransferases
46:
3957:10.1089/ars.2010.3208
3768:10.1101/lm.045112.117
2774:10.1101/gr.082701.108
1177:
1164:Transposable Elements
1049:
1010:
881:translesion synthesis
831:head and neck cancers
797:head and neck cancers
589:
505:
432:
380:
332:
228:
173:to the guanine base.
158:together in DNA. The
40:
3715:10.3390/genes8050141
3611:10.1128/IAI.00047-08
2618:10.1155/2016/2192853
2106:(18 November 2014).
1141:base excision repair
1054:(5mC) in neuron DNA.
1033:base excision repair
441:
389:
385:and the expected as
349:
264:Genomic distribution
254:base excision repair
202:
148:5'βCβphosphateβGβ3'
4190:2020PNAS..11719359Z
4184:(32): 19359β19366.
4109:2020PNAS..11719359Z
4103:(32): 19359β19366.
2817:(46): 75379β75393.
2502:2013Sci...339.1546V
2173:2002PNAS...99.3740T
1980:2006PNAS..103.1412S
1881:2002PNAS...99.4145M
1821:2001Sci...291.1304V
1755:2001Natur.409..860L
1539:2004PNAS..10113994H
1468:2001Natur.409..860L
1401:2001Natur.409..860L
1349:10.1101/gad.2037511
1283:2006PNAS..103.1412S
1209:DNA methylation age
965:synaptic plasticity
913:DNA methylation age
893:malignant neoplasms
879:due to error-prone
677:gene set enrichment
526:house-keeping genes
269:
134:CpG characteristics
4267:Molecular genetics
4006:10.4137/JEN.S39887
4000:(Suppl 1): 23β48.
3894:Front Mol Neurosci
3185:(2 Pt 1): 473β82.
3052:10.3892/or.9.3.529
2459:10.1101/gad.947102
2072:10.1093/nar/gni180
1533:(39): 13994β4001.
1181:
1056:
1017:
919:Unmethylated sites
592:
564:housekeeping genes
500:
497:length of sequence
427:
424:length of sequence
375:
336:
321:the human genome.
268:
223:
47:
3436:978-953-51-1114-6
2873:978-1-4419-9966-5
2668:10.1002/path.4132
2496:(6127): 1546β58.
2412:978-3-319-42057-8
2371:10.1002/ijc.24772
2119:978-0-8153-4432-2
2060:Nucleic Acids Res
2040:978-0-7637-1511-3
1815:(5507): 1304β51.
1749:(6822): 860β921.
1462:(6822): 860β921.
1395:(6822): 860β921.
1127:DNA demethylation
1123:DNA demethylation
1050:Demethylation of
1013:DNA demethylation
972:fear conditioning
829:occurs in 46% of
819:occurs in 48% of
809:occurs in 47% of
795:occurs in 62% of
655:5-methylcytosines
609:located near the
498:
464:
453:
425:
409:
398:
358:
313:
312:
146:is shorthand for
126:located near the
97:5-methylcytosines
82:5' β 3' direction
68:is followed by a
18:CpG dinucleotides
16:(Redirected from
4279:
4249:
4248:
4240:
4230:
4229:
4219:
4201:
4169:
4163:
4162:
4156:
4148:
4138:
4120:
4088:
4077:
4076:
4066:
4034:
4028:
4027:
4017:
3985:
3979:
3978:
3968:
3936:
3930:
3929:
3919:
3909:
3885:
3879:
3878:
3850:
3839:
3838:
3828:
3796:
3790:
3789:
3779:
3747:
3738:
3737:
3727:
3717:
3693:
3684:
3683:
3673:
3663:
3654:(12): e1002389.
3639:
3633:
3632:
3622:
3605:(5): 2123β2129.
3590:
3584:
3583:
3581:
3549:
3543:
3542:
3532:
3522:
3498:
3492:
3491:
3481:
3471:
3447:
3441:
3440:
3422:
3416:
3415:
3405:
3378:
3372:
3371:
3351:
3345:
3344:
3334:
3302:
3296:
3295:
3261:
3252:
3246:
3245:
3235:
3220:Int. J. Mol. Med
3211:
3205:
3204:
3194:
3179:Clin. Cancer Res
3170:
3164:
3163:
3119:
3113:
3112:
3102:
3070:
3064:
3063:
3035:
3029:
3028:
2992:
2986:
2985:
2975:
2951:
2945:
2944:
2934:
2902:
2896:
2895:
2885:
2851:
2845:
2844:
2834:
2802:
2796:
2795:
2785:
2745:
2739:
2738:
2728:
2696:
2690:
2689:
2679:
2647:
2641:
2640:
2630:
2620:
2596:
2590:
2589:
2579:
2569:
2541:
2532:
2531:
2521:
2478:
2472:
2471:
2461:
2434:
2425:
2424:
2390:
2384:
2383:
2373:
2349:
2343:
2342:
2324:
2300:
2294:
2293:
2283:
2246:
2240:
2239:
2211:
2205:
2204:
2194:
2184:
2152:
2146:
2145:
2139:
2131:
2100:
2094:
2093:
2083:
2051:
2045:
2044:
2028:
2018:
2012:
2011:
2001:
1991:
1974:(5): 1412β1417.
1959:
1948:
1947:
1919:
1913:
1912:
1902:
1892:
1849:
1843:
1842:
1832:
1793:
1787:
1786:
1776:
1766:
1764:10.1038/35057062
1731:
1725:
1724:
1714:
1690:
1684:
1683:
1673:
1638:
1632:
1631:
1625:
1621:
1619:
1611:
1577:
1571:
1570:
1560:
1550:
1514:
1508:
1507:
1489:
1479:
1477:10.1038/35057062
1447:
1441:
1440:
1422:
1412:
1410:10.1038/35057062
1377:
1371:
1370:
1360:
1324:
1315:
1314:
1304:
1294:
1262:
1253:
1252:
1224:
1052:5-Methylcytosine
1025:5-methylcytosine
976:long-term memory
909:epigenetic clock
907:(referred to as
905:biological clock
515:promoter regions
509:
507:
506:
501:
499:
496:
494:
489:
488:
476:
465:
462:
454:
451:
436:
434:
433:
428:
426:
423:
421:
410:
407:
399:
396:
384:
382:
381:
376:
359:
356:
292:
285:
270:
232:
230:
229:
224:
21:
4287:
4286:
4282:
4281:
4280:
4278:
4277:
4276:
4257:
4256:
4255:
4243:
4235:
4233:
4171:
4170:
4166:
4149:
4090:
4089:
4080:
4055:10.1038/nn.2666
4049:(11): 1319β23.
4036:
4035:
4031:
3987:
3986:
3982:
3951:(10): 2013β54.
3938:
3937:
3933:
3887:
3886:
3882:
3852:
3851:
3842:
3817:10.1038/nn.4194
3798:
3797:
3793:
3749:
3748:
3741:
3695:
3694:
3687:
3641:
3640:
3636:
3592:
3591:
3587:
3551:
3550:
3546:
3500:
3499:
3495:
3462:(8): e1000155.
3449:
3448:
3444:
3437:
3424:
3423:
3419:
3390:Mol. Cancer Res
3380:
3379:
3375:
3353:
3352:
3348:
3304:
3303:
3299:
3259:
3254:
3253:
3249:
3213:
3212:
3208:
3172:
3171:
3167:
3121:
3120:
3116:
3079:Mol. Cancer Res
3072:
3071:
3067:
3037:
3036:
3032:
2997:J. Clin. Pathol
2994:
2993:
2989:
2960:Mol. Cancer Res
2953:
2952:
2948:
2911:Mol. Cancer Res
2904:
2903:
2899:
2874:
2853:
2852:
2848:
2804:
2803:
2799:
2747:
2746:
2742:
2698:
2697:
2693:
2649:
2648:
2644:
2598:
2597:
2593:
2560:(9): e1001134.
2543:
2542:
2535:
2480:
2479:
2475:
2436:
2435:
2428:
2413:
2392:
2391:
2387:
2351:
2350:
2346:
2302:
2301:
2297:
2259:Nature Genetics
2248:
2247:
2243:
2213:
2212:
2208:
2154:
2153:
2149:
2132:
2120:
2102:
2101:
2097:
2053:
2052:
2048:
2041:
2020:
2019:
2015:
1961:
1960:
1951:
1921:
1920:
1916:
1851:
1850:
1846:
1795:
1794:
1790:
1733:
1732:
1728:
1692:
1691:
1687:
1662:10.1038/nrg2529
1640:
1639:
1635:
1622:
1612:
1600:
1579:
1578:
1574:
1516:
1515:
1511:
1449:
1448:
1444:
1381:Lander, Eric S.
1379:
1378:
1374:
1343:(10): 1010β22.
1326:
1325:
1318:
1264:
1263:
1256:
1226:
1225:
1221:
1217:
1199:
1190:
1172:
1160:
1121:formation. The
1080:glycosidic bond
1005:
949:
921:
901:
877:DNA replication
706:
663:
651:
621:Distal promoter
603:
598:
596:DNA methylation
584:
480:
463:number of
452:number of
439:
438:
408:number of
397:number of
387:
386:
357:number of
347:
346:
327:
266:
200:
199:
187:
141:
136:
57:are regions of
35:
32:
23:
22:
15:
12:
11:
5:
4285:
4283:
4275:
4274:
4269:
4259:
4258:
4254:
4253:
4232:
4231:
4164:
4078:
4029:
3994:J Exp Neurosci
3980:
3931:
3880:
3861:(9): 1163β71.
3840:
3791:
3762:(7): 278β288.
3739:
3685:
3634:
3585:
3564:(6): 882β895.
3558:Molecular Cell
3544:
3493:
3442:
3435:
3417:
3373:
3356:Anticancer Res
3346:
3317:(4): 1151β62.
3297:
3247:
3226:(5): 1268β74.
3206:
3165:
3114:
3085:(11): 1710β7.
3065:
3030:
2987:
2946:
2917:(4): 699β712.
2897:
2872:
2846:
2797:
2740:
2691:
2662:(5): 697β704.
2642:
2591:
2533:
2473:
2426:
2411:
2385:
2364:(8): 1944β54.
2358:Int. J. Cancer
2344:
2315:(5): 773β786.
2295:
2272:10.1038/ng.298
2266:(2): 178β186.
2241:
2222:(4): 192β199.
2206:
2147:
2118:
2104:Alberts, Bruce
2095:
2046:
2039:
2013:
1949:
1930:(2): 261β282.
1914:
1863:(April 2002).
1844:
1788:
1726:
1685:
1656:(7): 478β488.
1633:
1624:|journal=
1598:
1572:
1509:
1442:
1372:
1316:
1254:
1218:
1216:
1213:
1212:
1211:
1206:
1198:
1195:
1189:
1186:
1171:
1168:
1159:
1156:
1070:) to generate
1015:at a CpG site.
1011:Initiation of
1004:
1001:
988:gene promoters
948:
945:
920:
917:
900:
897:
875:errors during
799:and in 42% of
705:
702:
693:messenger RNAs
662:
659:
650:
647:
602:
599:
594:Main article:
583:
580:
541:CG suppression
493:
487:
483:
479:
475:
471:
468:
460:
457:
449:
446:
420:
416:
413:
405:
402:
394:
374:
371:
368:
365:
362:
354:
326:
323:
311:
310:
294:
293:
286:
278:
277:
274:
265:
262:
222:
219:
216:
213:
210:
207:
186:
183:
140:
137:
135:
132:
33:
24:
14:
13:
10:
9:
6:
4:
3:
2:
4284:
4273:
4270:
4268:
4265:
4264:
4262:
4252:
4247:
4242:
4238:
4227:
4223:
4218:
4213:
4209:
4205:
4200:
4195:
4191:
4187:
4183:
4179:
4175:
4168:
4165:
4160:
4154:
4146:
4142:
4137:
4132:
4128:
4124:
4119:
4114:
4110:
4106:
4102:
4098:
4094:
4087:
4085:
4083:
4079:
4074:
4070:
4065:
4060:
4056:
4052:
4048:
4044:
4043:Nat. Neurosci
4040:
4033:
4030:
4025:
4021:
4016:
4011:
4007:
4003:
3999:
3995:
3991:
3984:
3981:
3976:
3972:
3967:
3962:
3958:
3954:
3950:
3946:
3942:
3935:
3932:
3927:
3923:
3918:
3913:
3908:
3903:
3899:
3895:
3891:
3884:
3881:
3876:
3872:
3868:
3864:
3860:
3856:
3849:
3847:
3845:
3841:
3836:
3832:
3827:
3822:
3818:
3814:
3811:(1): 102β10.
3810:
3806:
3805:Nat. Neurosci
3802:
3795:
3792:
3787:
3783:
3778:
3773:
3769:
3765:
3761:
3757:
3753:
3746:
3744:
3740:
3735:
3731:
3726:
3721:
3716:
3711:
3707:
3703:
3702:Genes (Basel)
3699:
3692:
3690:
3686:
3681:
3677:
3672:
3667:
3662:
3657:
3653:
3649:
3645:
3638:
3635:
3630:
3626:
3621:
3616:
3612:
3608:
3604:
3600:
3599:Infect. Immun
3596:
3589:
3586:
3580:
3575:
3571:
3567:
3563:
3559:
3555:
3548:
3545:
3540:
3536:
3531:
3526:
3521:
3516:
3512:
3508:
3507:PLOS Genetics
3504:
3497:
3494:
3489:
3485:
3480:
3475:
3470:
3465:
3461:
3457:
3456:PLOS Genetics
3453:
3446:
3443:
3438:
3432:
3428:
3421:
3418:
3413:
3409:
3404:
3399:
3396:(4): 517β24.
3395:
3391:
3387:
3383:
3377:
3374:
3369:
3365:
3362:(7): 2453β9.
3361:
3357:
3350:
3347:
3342:
3338:
3333:
3328:
3324:
3320:
3316:
3312:
3311:Am. J. Pathol
3308:
3301:
3298:
3293:
3289:
3285:
3281:
3277:
3273:
3270:(1): 111β20.
3269:
3265:
3258:
3251:
3248:
3243:
3239:
3234:
3229:
3225:
3221:
3217:
3210:
3207:
3202:
3198:
3193:
3188:
3184:
3180:
3176:
3169:
3166:
3161:
3157:
3153:
3149:
3145:
3141:
3138:(2): 445β51.
3137:
3133:
3129:
3128:Belldegrun AS
3125:
3118:
3115:
3110:
3106:
3101:
3096:
3092:
3088:
3084:
3080:
3076:
3069:
3066:
3061:
3057:
3053:
3049:
3046:(3): 529β32.
3045:
3041:
3034:
3031:
3026:
3022:
3018:
3014:
3010:
3006:
3003:(7): 607β12.
3002:
2998:
2991:
2988:
2983:
2979:
2974:
2969:
2966:(3): 470β82.
2965:
2961:
2957:
2950:
2947:
2942:
2938:
2933:
2928:
2924:
2920:
2916:
2912:
2908:
2901:
2898:
2893:
2889:
2884:
2879:
2875:
2869:
2865:
2861:
2857:
2850:
2847:
2842:
2838:
2833:
2828:
2824:
2820:
2816:
2812:
2808:
2801:
2798:
2793:
2789:
2784:
2779:
2775:
2771:
2768:(1): 92β105.
2767:
2763:
2759:
2755:
2751:
2744:
2741:
2736:
2732:
2727:
2722:
2718:
2714:
2710:
2706:
2702:
2695:
2692:
2687:
2683:
2678:
2673:
2669:
2665:
2661:
2657:
2653:
2646:
2643:
2638:
2634:
2629:
2624:
2619:
2614:
2610:
2606:
2602:
2595:
2592:
2587:
2583:
2578:
2573:
2568:
2563:
2559:
2555:
2551:
2547:
2540:
2538:
2534:
2529:
2525:
2520:
2515:
2511:
2507:
2503:
2499:
2495:
2491:
2487:
2483:
2477:
2474:
2469:
2465:
2460:
2455:
2451:
2447:
2443:
2439:
2433:
2431:
2427:
2422:
2418:
2414:
2408:
2404:
2400:
2396:
2389:
2386:
2381:
2377:
2372:
2367:
2363:
2359:
2355:
2348:
2345:
2340:
2336:
2332:
2328:
2323:
2318:
2314:
2310:
2306:
2299:
2296:
2291:
2287:
2282:
2277:
2273:
2269:
2265:
2261:
2260:
2255:
2251:
2245:
2242:
2237:
2233:
2229:
2225:
2221:
2217:
2210:
2207:
2202:
2198:
2193:
2188:
2183:
2178:
2174:
2170:
2167:(6): 3740β5.
2166:
2162:
2158:
2151:
2148:
2143:
2137:
2129:
2125:
2121:
2115:
2111:
2110:
2105:
2099:
2096:
2091:
2087:
2082:
2077:
2073:
2069:
2065:
2061:
2057:
2050:
2047:
2042:
2036:
2032:
2027:
2026:
2017:
2014:
2009:
2005:
2000:
1995:
1990:
1985:
1981:
1977:
1973:
1969:
1965:
1958:
1956:
1954:
1950:
1945:
1941:
1937:
1933:
1929:
1925:
1918:
1915:
1910:
1906:
1901:
1896:
1891:
1886:
1882:
1878:
1875:(7): 4145β6.
1874:
1870:
1866:
1862:
1858:
1855:, Sutton GG,
1854:
1848:
1845:
1840:
1836:
1831:
1826:
1822:
1818:
1814:
1810:
1806:
1802:
1798:
1792:
1789:
1784:
1780:
1775:
1774:2027.42/62798
1770:
1765:
1760:
1756:
1752:
1748:
1744:
1740:
1736:
1730:
1727:
1722:
1718:
1713:
1708:
1704:
1700:
1696:
1689:
1686:
1681:
1677:
1672:
1667:
1663:
1659:
1655:
1651:
1650:Nat Rev Genet
1647:
1643:
1637:
1634:
1629:
1617:
1609:
1605:
1601:
1599:3-540-29114-8
1595:
1591:
1587:
1583:
1576:
1573:
1568:
1564:
1559:
1554:
1549:
1544:
1540:
1536:
1532:
1528:
1524:
1520:
1513:
1510:
1505:
1501:
1497:
1493:
1488:
1487:2027.42/62798
1483:
1478:
1473:
1469:
1465:
1461:
1457:
1453:
1446:
1443:
1438:
1434:
1430:
1426:
1421:
1420:2027.42/62798
1416:
1411:
1406:
1402:
1398:
1394:
1390:
1386:
1382:
1376:
1373:
1368:
1364:
1359:
1354:
1350:
1346:
1342:
1338:
1334:
1330:
1323:
1321:
1317:
1312:
1308:
1303:
1298:
1293:
1288:
1284:
1280:
1277:(5): 1412β7.
1276:
1272:
1268:
1261:
1259:
1255:
1250:
1246:
1242:
1238:
1234:
1230:
1223:
1220:
1214:
1210:
1207:
1204:
1201:
1200:
1196:
1194:
1187:
1185:
1176:
1169:
1167:
1165:
1157:
1155:
1152:
1150:
1146:
1142:
1138:
1134:
1130:
1128:
1124:
1120:
1116:
1111:
1109:
1105:
1101:
1097:
1093:
1089:
1085:
1081:
1077:
1073:
1069:
1065:
1061:
1053:
1048:
1044:
1042:
1038:
1034:
1030:
1026:
1022:
1014:
1009:
1002:
1000:
998:
993:
989:
985:
981:
977:
973:
968:
966:
961:
958:
957:methyl groups
954:
946:
944:
942:
938:
934:
930:
926:
918:
916:
914:
910:
906:
898:
896:
894:
890:
886:
882:
878:
874:
869:
867:
863:
859:
855:
851:
847:
846:
841:
840:
834:
832:
828:
827:
822:
818:
817:
812:
808:
807:
802:
798:
794:
793:
788:
787:
782:
781:
776:
775:
770:
768:
764:
760:
756:
752:
748:
744:
740:
736:
732:
728:
724:
720:
716:
711:
703:
701:
697:
694:
690:
684:
682:
678:
673:
669:
660:
658:
656:
648:
646:
644:
640:
636:
632:
628:
627:
622:
618:
616:
612:
608:
600:
597:
588:
581:
579:
577:
573:
569:
565:
560:
558:
554:
550:
546:
545:coding region
542:
536:
534:
529:
527:
523:
518:
516:
511:
491:
485:
477:
473:
466:
458:
455:
418:
411:
403:
400:
369:
366:
363:
360:
344:
340:
334:detrimental).
331:
324:
322:
319:
308:
304:
300:
295:
291:
287:
284:
280:
279:
271:
263:
261:
259:
255:
251:
247:
243:
239:
238:mutation rate
234:
217:
214:
211:
208:
205:
197:
193:
184:
182:
180:
176:
172:
168:
165:
161:
157:
153:
149:
145:
138:
133:
131:
129:
125:
120:
118:
114:
110:
106:
102:
98:
94:
89:
87:
83:
79:
75:
71:
67:
64:
60:
56:
52:
44:
39:
30:
19:
4181:
4177:
4167:
4153:cite journal
4100:
4096:
4046:
4042:
4032:
3997:
3993:
3983:
3948:
3944:
3934:
3897:
3893:
3883:
3858:
3855:Cell. Signal
3854:
3808:
3804:
3794:
3759:
3755:
3705:
3701:
3651:
3647:
3637:
3602:
3598:
3588:
3561:
3557:
3547:
3510:
3506:
3496:
3459:
3455:
3445:
3426:
3420:
3393:
3389:
3376:
3359:
3355:
3349:
3314:
3310:
3300:
3267:
3263:
3250:
3223:
3219:
3209:
3182:
3178:
3168:
3135:
3131:
3117:
3082:
3078:
3068:
3043:
3039:
3033:
3000:
2996:
2990:
2963:
2959:
2949:
2914:
2910:
2900:
2855:
2849:
2814:
2810:
2800:
2765:
2761:
2743:
2711:(1): 66β81.
2708:
2704:
2694:
2659:
2655:
2645:
2608:
2605:Dis. Markers
2604:
2594:
2557:
2553:
2493:
2489:
2482:Vogelstein B
2476:
2449:
2445:
2394:
2388:
2361:
2357:
2347:
2312:
2308:
2298:
2263:
2257:
2244:
2219:
2216:Trends Genet
2215:
2209:
2164:
2160:
2150:
2108:
2098:
2066:(20): e176.
2063:
2059:
2049:
2024:
2016:
1971:
1967:
1927:
1923:
1917:
1872:
1868:
1859:, Adams MD,
1847:
1812:
1808:
1799:, Adams MD,
1791:
1746:
1742:
1729:
1702:
1698:
1688:
1653:
1649:
1636:
1581:
1575:
1530:
1526:
1512:
1459:
1455:
1445:
1392:
1388:
1375:
1340:
1336:
1274:
1270:
1232:
1228:
1222:
1191:
1182:
1161:
1153:
1131:
1112:
1088:(AID/APOBEC)
1057:
1018:
969:
962:
951:In mammals,
950:
922:
902:
870:
853:
849:
843:
837:
835:
824:
814:
804:
790:
784:
778:
772:
713:
707:
698:
685:
664:
652:
634:
624:
619:
604:
561:
537:
530:
519:
512:
338:
337:
314:
235:
194:, a pair of
188:
178:
174:
167:base-pairing
163:
159:
147:
143:
142:
121:
105:methyl group
90:
54:
50:
48:
42:
41:a CpG site,
3513:(7): e110.
3264:Cancer Lett
2452:(1): 6β21.
2250:Irizarry RA
1327:Deaton AM,
1023:), forming
992:hippocampus
980:hippocampus
955:(which add
572:deamination
549:methylation
533:Alu repeats
339:CpG islands
325:CpG islands
242:deamination
196:nucleotides
156:nucleosides
113:epigenetics
107:are called
103:that add a
86:CpG islands
4261:Categories
3756:Learn. Mem
3708:(5): 141.
3648:PLOS Genet
3040:Oncol. Rep
2811:Oncotarget
2762:Genome Res
2554:PLOS Genet
1517:Hwang DG,
1215:References
885:epigenetic
873:mutational
672:hitchhiker
615:CpG island
557:imprinting
303:CpG island
276:GpC sites
273:CpG sites
258:transition
192:GC content
139:Definition
93:methylated
80:along its
66:nucleotide
4208:1091-6490
4127:1091-6490
3382:Kastan MB
3124:Horvath S
2754:Bartel DP
2656:J. Pathol
2446:Genes Dev
2136:cite book
2128:887605755
1861:Venter JC
1797:Venter JC
1735:Lander ES
1705:: 47β70.
1642:Arnheim N
1626:ignored (
1616:cite book
1496:0028-0836
1429:1476-4687
1337:Genes Dev
1235:: 143β9.
1179:is found.
1021:CpG sites
933:monocytes
689:microRNAs
681:gene sets
643:microRNAs
607:promoters
522:promoters
404:∗
221:%
209:×
152:phosphate
124:promoters
51:CpG sites
4226:32719115
4145:32719115
4073:20975755
4024:27625575
3975:20649473
3926:29875631
3875:27251462
3835:26656643
3786:28620075
3734:28505093
3680:22174693
3629:18332208
3539:17616978
3488:18704159
3412:18403632
3384:(2008).
3368:19596913
3341:12651607
3292:44644467
3284:15922863
3242:24590400
3201:15701830
3160:22165252
3152:16879693
3109:19010819
3060:11956622
3017:23486608
2982:25563294
2941:25828893
2892:22956494
2841:27683114
2792:18955434
2756:(2009).
2750:Burge CB
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