366:(5fC) and 5-carboxylcytosine (5caC). Thymine-DNA glycosylase (TDG) recognizes the intermediate bases 5fC and 5caC and cleaves the glycosidic bond resulting in an apyrimidinic site (AP site). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex (AID/APOBEC) to form 5-hydroxymethyluracil (5hmU). 5mC can also be converted to thymine (Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Nei-Like DNA glycosylase 1 (NEIL1), or methyl-CpG binding protein 4 (MBD4). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt).
327:. This included more than 2,000 differentially methylated genes at 24 hours after training, with over 500 genes being demethylated. The hippocampus region of the brain is where contextual fear memories are first stored (see figure of the brain, this section), but this storage is transient and does not remain in the hippocampus. In rats contextual fear conditioning is abolished when the hippocampus is subjected to hippocampectomy just 1 day after conditioning, but rats retain a considerable amount of contextual fear when a long delay (28 days) is imposed between the time of conditioning and the time of hippocampectomy.
483:
450:. TET3o only occurs in oocytes and neurons and was not expressed in embryonic stem cells or in any other cell type or adult mouse tissue tested. Whereas TET1 expression can barely be detected in oocytes and zygotes, and TET2 is only moderately expressed, the TET3 variant TET3o shows extremely high levels of expression in oocytes and zygotes, but is nearly absent at the 2-cell stage. It is possible that TET3o, high in neurons, oocytes and zygotes at the one cell stage, is the major TET enzyme utilized when very large scale rapid demethylations occur in these cells.
1004:
130:
355:
236:
549:. OGG1 finds 8-OHdG by sliding along the linear DNA at 1,000 base pairs of DNA in 0.1 seconds. OGG1 very rapidly finds 8-OHdG. OGG1 proteins bind to oxidatively damaged DNA with a half maximum time of about 6 seconds. When OGG1 finds 8-OHdG it changes conformation and complexes with 8-OHdG in the binding pocket of OGG1. OGG1 does not immediately act to remove the 8-OHdG. Half maximum removal of 8-OHdG takes about 30 minutes in
612:(IEG). The defining characteristic of IEGs is the rapid and transient up-regulation—within minutes—of their mRNA levels independent of protein synthesis. EGR1 can rapidly be induced by neuronal activity. In adulthood, EGR1 is expressed widely throughout the brain, maintaining baseline expression levels in several key areas of the brain including the
304:
806:, as somatic epitypes can potentially be altered after an organism has left the developmental stage of life. During somatic cell nuclear transfer, the oocyte turns off tissue specific genes in the somatic cell nucleus and turns back on embryonic specific genes. This process has been shown through cloning, as seen through
995:(DMNTs), starting in the maturation phase and into the stabilization stage. Once the epigenetic memory of the cell is lost, the possibility of differentiation into the three germ layers is achieved. This is considered a fully reprogrammed cell as it can be passaged without reverting to its original somatic cell type.
719:. The cell morphology can directly affect the reprogramming process as the cell is modifying itself to prepare for the gene expression of pluripotency. The main indicator that the initiation phase has completed is that the first genes associated with pluripotency are expressed. This includes the expression of
1278:
The properties of cells obtained after reprogramming can vary significantly, in particular among iPSCs. Factors leading to variation in the performance of reprogramming and functional features of end products include genetic background, tissue source, reprogramming factor stoichiometry and stressors
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is a commonly used factor when reprogramming cells into not only iPSCs, but also other cells. C/EBPα has shown itself to be a single transacting factor during direct reprogramming of a lymphoid cell into a myeloid cell. C/EBPα is considered a 'path breaker' to aid in preparing the cell for intake of
438:
usage which gives rise to a short transcript and a truncated protein designated TET1s. The isoforms of TET3 are the full length form TET3FL, a short form splice variant TET3s, and a form that occurs in oocytes and neurons designated TET3o. TET3o is created by alternative promoter use and contains an
314:
and memory have levels of permanence, differing from other mental processes such as thought, language, and consciousness, which are temporary in nature. Learning and memory can be either accumulated slowly (multiplication tables) or rapidly (touching a hot stove), but once attained, can be recalled
645:, who in 1962 demonstrated that differentiated somatic cells could be reprogrammed back into an embryonic state when he managed to obtain swimming tadpoles following the transfer of differentiated intestinal epithelial cells into enucleated frog eggs. For this achievement he received the 2012
339:. Stage 1: Recruitment. The enzymes needed for reprogramming are recruited to genome sites that require demethylation or methylation. Stage 2: Implementation. The initial enzymatic reactions take place. In the case of methylation, this is a short step that results in the methylation of
781:
632:
regions of both proteins, independently of association with DNA. EGR1 recruits TET1s to genomic regions flanking EGR1 binding sites. In the presence of EGR1, TET1s is capable of locus-specific demethylation and activation of the expression of downstream genes regulated by EGR1.
912:
The maturation phase begins at the end of the initiation phase, when the first pluripotent genes are expressed. The cell is preparing itself to be independent from the defined factors, that started the reprogramming process. The first genes to be detected in iPSCs are
474:
CGIs. TET2 does not have an affinity for 5-methylcytosine in DNA. The CXXC domain of the full-length TET3, which is the predominant form expressed in neurons, binds most strongly to CpGs where the C was converted to 5-carboxycytosine (5caC). However, it also binds to
844:. The fused cells allow for otherwise silenced genes to become reactivated and expressive. As the genes are reactivated, the cells can re-differentiate. There are instances where transcriptional factors, such as the Yamanaka factors, are still needed to aid in
224:. Now the cells are rapidly proliferating and beginning demethylation in two waves. In the first wave, demethylation is by replicative dilution, but in the second wave demethylation is by an active process. The second wave leads to demethylation of specific
746:
to another, the genes associated with each cell type begin to be upregulated and downregulated accordingly. This can either occur through direct cell reprogramming or creating an intermediate, such as a iPSC, and differentiating into the desired cell type.
857:
45:
Reprogrammings that are both large scale (10% to 100% of epigenetic marks) and rapid (hours to a few days) occur at three life stages of mammals. Almost 100% of epigenetic marks are reprogrammed in two short periods early in development after
1146:
is a gene used in maintaining pluripotency in stem cells. Oct4 and Sox2 work together to regulate hundreds of genes utilized in pluripotency. However, Sox2 is not the only possible Sox family member to participate in gene regulation with Oct4
823:
787:. The nucleus of a somatic cell is transferred into an oocyte that has had its original nucleus removed. That oocyte will take in the genetic material from the somatic cell and divide into a totipotent cell. Created with BioRender.com
434:. The full-length canonical TET1 isoform appears virtually restricted to early embryos, embryonic stem cells and primordial germ cells (PGCs). The dominant TET1 isoform in most somatic tissues, at least in the mouse, arises from
653:. Yamanaka was the first to demonstrate (in 2006) that this somatic cell nuclear transfer or oocyte-based reprogramming process (see below), that Gurdon discovered, could be recapitulated (in mice) by defined factors (
266:. There is asymmetry at this point: the male pronucleus undergoes a quick and active demethylation. Meanwhile the female pronucleus is demethylated passively during consecutive cell divisions. The process of
219:
The newly formed primordial germ cells (PGC) in the implanted embryo devolve from the somatic cells. At this point the PGCs have high levels of methylation. These cells migrate from the epiblast toward the
702:
activity, genetic and morphological markers were used as a way to determine what phase of reprogramming was occurring. Reprogramming is defined into three phase: initiation, maturation, and stabilization.
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With the discovery that cell fate could be altered, the question of what progression of events occurs signifies a cell undergoing reprogramming. As the final product of iPSC reprogramming was similar in
3695:
Paull D, Sevilla A, Zhou H, Hahn AK, Kim H, Napolitano C, et al. (September 2015). "Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells".
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of guanine bases adjacent to 5-methylcytosine. TET1 binds (is recruited to) the OGG1 bound to 8-OHdG (see figure). This likely allows TET1 to demethylate an adjacent methylated cytosine. When human
628:
5′-GCGTGGGCG-3′ and 5'-GCGGGGGCGG-3′ and these motifs occur primarily in promoter regions of genes. The short isoform TET1s is expressed in the brain. EGR1 and TET1s form a complex mediated by the
3327:
Bueno C, Sardina JL, Di
Stefano B, Romero-Moya D, Muñoz-López A, Ariza L, et al. (March 2016). "Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα".
1098:
was C/EBPα. MyoD and C/EBPα are examples of a small number of single factors that can transform cells. More often, a combination of transcription factors work in conjunction to reprogram a cell.
2284:"Catalytic and DNA-binding properties of the human Ogg1 DNA N-glycosylase/AP lyase: biochemical exploration of H270, Q315 and F319, three amino acids of the 8-oxoguanine-binding pocket"
2832:
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (November 2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors".
358:
Demethylation of 5-methylcytosine. Demethylation of 5-methylcytosine (5mC) in neuron DNA. As reviewed in 2018, in brain neurons, 5mC is oxidized by a TET dioxygenase to generate
868:, epigenetic markers, and other small molecules or a combination of these can induce cellular reprogramming by causing the expression of other genes. Created with BioRender.com
711:
The initiation phase is associated with the downregulation of cell type specific genes and the upregulation of pluripotent genes. As the cells move towards pluripotency, the
351:. The intermediate products of demethylation are catalysed by specific enzymes of the base excision DNA repair pathway that finally restore cystosine in the DNA sequence.
81:, with demethylation and remethylation occurring each time. Demethylation during early embryogenesis occurs in the preimplantation period. After a sperm fertilizes an
1030:
are passaged, the epigenetic memory of the cells diminishes and the cells gradually want to differentiate into any cell type rather than the original somatic cell type.
251:, maternal and paternal genomes are differentially marked and must be properly reprogrammed every time they pass through the germline. Therefore, during the process of
73:
patterns are largely erased and then re-established during early embryonic development. Almost all of the methylations from the parents are erased, first during early
1136:
and tumors. The use of Oct4 even in small increases allows for the start differentiation into pluripotency. Oct4 works in conjecture with Sox2 for the expression of
904:
and other small molecule-driven processes has been utilized as a means of increasing the efficiency of the differentiation from somatic cells to pluripotency.
624:. This expression is linked to control of cognition, emotional response, social behavior and sensitivity to reward. EGR1 binds to DNA at sites with the
872:
Unlike nuclear transfer and cell fusion, defined factors do not require a full genome, only reprogramming factors. These reprogramming factors include
374:
in the demethylation of 5-methylcytosine to form cytosine. As reviewed in 2018, 5mC is very often initially oxidized by TET dioxygenases to generate
295:
manipulation of pre-implantation embryos has been shown to disrupt methylation patterns at imprinted loci and plays a crucial role in cloned animals.
204:, going from 12% to 62% methylation, and reaching maximum level after implantation in the uterus. By day seven after fertilization, the newly formed
3535:
Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, et al. (July 2007). "Non-transcriptional control of DNA replication by c-Myc".
2441:"Mapping structurally defined guanine oxidation products along DNA duplexes: influence of local sequence context and endogenous cytosine methylation"
1185:
reprogramming. When being utilized in cellular reprogramming, Klf4 prevents cell division of damaged cells using its apoptotic ability, and aids in
880:, epigenetic markers, and other small molecules. The original transcription factors, that lead to iPSC development, discovered by Yamanaka include
936:
As reprogramming efficiency has proven to be a variable and low efficiency process, not all the cells complete the maturation phase and achieve
2080:
Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress induced DNA demethylation".
728:
590:, 8-OHdG increased in DNA by 3.5-fold and this caused large scale demethylation of 5-methylcytosine to about 20% of its initial level in DNA.
274:
and likely other DNA-repair-based mechanisms. Despite the global nature of this process, there are certain sequences that avoid it, such as
984:
184:, about 40% of its CpG sites are methylated. Demethylation of the maternal chromosome largely takes place by blockage of the methylating
3228:
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (February 1997). "Viable offspring derived from fetal and adult mammalian cells".
961:
937:
695:
2392:"A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA"
1270:
the OSKM factors and specific transcription events. C/EBPα has also been shown to increase the efficiency of the reprogramming events.
3488:"Sox2 and Oct-3/4: a versatile pair of master regulators that orchestrate the self-renewal and pluripotency of embryonic stem cells"
275:
38:, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of
952:, proteins, and different combinations of the OSKM factors have started to lead towards a higher efficiency rate of reprogramming.
262:
After fertilization, the paternal and maternal genomes are demethylated in order to erase their epigenetic signatures and acquire
109:
stage of the embryo. Another period of rapid and almost complete demethylation occurs during gametogenesis within the primordial
896:(OSKM factors). Although the OSKM factors have been shown to induce and aid in pluripotency, other transcription factors such as
511:
431:
427:
324:
188:
from acting on maternal-origin DNA and by dilution of the methylated maternal DNA during replication (red line in Figure). The
2664:
2613:
Gurdon JB (December 1962). "The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles".
983:
and loss of the cell’s epigenetic memory. The epigenetic memory of a cell is reset by the changes in DNA methylation, using
1397:"Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse"
1123:
1039:
1027:
796:
784:
670:
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and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC as shown in the previous figure.
243:
After fertilization some cells of the newly formed embryo migrate to the germinal ridge and will eventually become the
3754:
1638:"Epigenetic reprogramming in early embryonic development: effects of in-vitro production and somatic nuclear transfer"
482:
546:
499:
113:(PGCs). Other than the PGCs, in the post-implantation stage, methylation patterns in somatic cells are stage- and
303:
1186:
972:
106:
3271:
Pereira CF, Terranova R, Ryan NK, Santos J, Morris KJ, Cui W, et al. (September 2008). Roopenian DC (ed.).
510:
targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits
1174:
613:
447:
414:. AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt).
348:
319:
create an especially strong long-term memory. At 24 h after training, 9.17% of the genes in the rat genomes of
2725:
2640:
1882:"Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration"
1247:
1223:
646:
561:
466:
except when recruited. Without recruitment or targeting, TET1 predominantly binds to high CG promoters and
383:
375:
359:
2665:"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors"
2235:"DNA ligase III acts as a DNA strand break sensor in the cellular orchestration of DNA strand break repair"
1215:
918:
897:
724:
674:
542:
527:
507:
129:
2176:"A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA"
1288:
992:
229:
228:. At this point the PGC genomes display the lowest levels of DNA methylation of any cells in the entire
1597:"Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos"
1548:"Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers"
1034:
Reprogramming can also be induced artificially through the introduction of exogenous factors, usually
354:
3749:
3648:
3544:
3273:"Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2"
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20:
1199:, and in certain conditions can become cancer causing. In cellular reprogramming, c-Myc is used for
1126:(iPSCs). Within the following year, these factors were used to induce human fibroblasts into iPSCs.
1003:
1831:"The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders"
1777:"The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders"
1218:(NANOG) is a transcription factor used to aid in the efficiency of generating iPSCs by maintaining
1133:
1051:
3136:"Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension"
2776:"Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension"
1078:
One of the first transacting factors discovered to change a cell was found in a myoblast when the
394:(AP site). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by
3720:
3617:
3568:
3362:
3210:
3116:
2931:
2867:
2756:
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1338:
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498:-pG, (5mCpG). Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming
248:
1122:) were initially discovered by Yamanaka in 2006, by the induction of a mouse fibroblast into an
780:
490:. In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides (
235:
180:
in six hours by an active process, before DNA replication (blue line in Figure). In the mature
3185:
Mathers JC (June 2006). "Nutritional modulation of ageing: genomic and epigenetic approaches".
2555:"EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity"
2495:"The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders"
2117:"EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity"
196:(black line in Figure). Methylation begins to increase at 3.5 days after fertilization in the
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The stabilization phase refers to the processes in the cell that occur after the cell reaches
933:. Once the cell is independent, the maturation phase ends and the stabilization phase begins.
580:
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in DNA. Two of the proteins shown to recruit a TET enzyme to a methylated cytosine in DNA are
316:
267:
177:
90:
3434:
Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, et al. (December 2012).
1313:
Reik W, Dean W, Walter J (August 2001). "Epigenetic reprogramming in mammalian development".
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of the paternal DNA and slower demethylation of the maternal DNA occurs until formation of a
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Deplus R, Delatte B, Schwinn MK, Defrance M, Méndez J, Murphy N, et al. (March 2013).
1728:"Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review"
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Heurtier V, Owens N, Gonzalez I, Mueller F, Proux C, Mornico D, et al. (March 2019).
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1373:
803:
691:
650:
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387:
378:(5hmC). In successive steps (see Figure) TET enzymes further hydroxylate 5hmC to generate
336:
286:
279:
256:
193:
150:
70:
59:
35:
16:
Erasure and remodeling of epigenetic marks during mammalian development or in cell culture
2390:
Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, et al. (May 2001).
2331:
Lan L, Nakajima S, Oohata Y, Takao M, Okano S, Masutani M, et al. (September 2004).
3652:
3548:
3241:
3096:
2966:
2570:
2348:
2191:
2132:
2026:"TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS"
1552:
Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences
545:(OGG1) catalyses the first step in base excision repair of the oxidatively damaged base
398:(AID/APOBEC) deaminases to form 5-hydroxymethyluracil (5hmU) or 5mC can be converted to
216:. At this point the PGCs have about the same level of methylation as the somatic cells.
3669:
3636:
3586:
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ (March 2005).
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Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (2007-12-06).
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19:
This article is about the epigenetic phenomenon. For the writing of computer code, see
3057:
3030:
2949:
Downing TL, Soto J, Morez C, Houssin T, Fritz A, Yuan F, et al. (December 2013).
2367:
2332:
2308:
2283:
1880:
Jin SG, Zhang ZM, Dunwell TL, Harter MR, Wu X, Johnson J, et al. (January 2016).
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1637:
833:, which can then have the nuclease fuse, creating a hybrid. Created with BioRender.com
289:. Remethylation is needed again to differentiate the embryo into a complete organism.
66:
of the hippocampus can be rapidly altered during formation of a strong fear memory.
3738:
2760:
2416:
2391:
1499:"A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming"
1091:
811:
252:
221:
173:
78:
74:
47:
2935:
2439:
Ming X, Matter B, Song M, Veliath E, Shanley R, Jones R, Tretyakova N (March 2014).
1743:
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is part of the core regulatory genes needed for pluripotency, as it is seen in both
3744:
3724:
3621:
3572:
3214:
3120:
2871:
2699:
1595:
Mann MR, Chung YG, Nolen LD, Verona RI, Latham KE, Bartolomei MS (September 2003).
1219:
1182:
1095:
1063:
1059:
969:
845:
841:
830:
743:
370:
The Figure in this section indicates the central roles of ten-eleven translocation
213:
142:
3366:
3083:
Hochedlinger K, Jaenisch R (June 2006). "Nuclear reprogramming and pluripotency".
2744:
2333:"In situ analysis of repair processes for oxidative DNA damage in mammalian cells"
2093:
1613:
1596:
3637:"The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells"
3289:
3134:
Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (2006).
2001:
1984:
1897:
900:, LIN25, TRA-1-60, and C/EBPα aid in the efficiency of reprogramming. The use of
3604:
3587:
988:
837:
826:
807:
755:
642:
519:
459:
423:
371:
362:(5hmC). In successive steps a TET enzyme further hydroxylates 5hmC to generate
320:
283:
263:
259:
patterns erased and re-established based on the sex of the transmitting parent.
31:
3660:
3451:
3402:
2845:
2791:
2683:
2578:
2337:
Proceedings of the
National Academy of Sciences of the United States of America
2180:
Proceedings of the
National Academy of Sciences of the United States of America
2141:
1983:
Zhang W, Xia W, Wang Q, Towers AJ, Chen J, Gao R, et al. (December 2016).
1514:
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1200:
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673:(iPSCs). Other combinations of genes have also been used, including LIN25 and
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467:
440:
197:
98:
3047:
2511:
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1950:
1847:
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2200:
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1227:
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1047:
1007:
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silencing marks the start of the cell becoming independent from the induced
926:
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244:
205:
138:
118:
110:
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3066:
2992:
2927:
2863:
2809:
2752:
2691:
2626:
2596:
2530:
2474:
2425:
2376:
2317:
2268:
2219:
2160:
2101:
2059:
2041:
2010:
1969:
1915:
1866:
1812:
1761:
1712:
1663:
1622:
1581:
1563:
1546:
Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W (January 2013).
1532:
1483:
1432:
1381:
1334:
1159:
also participate, as the Sox protein is redundant throughout the stem cell
814:. Notably, these events have shown that cell fate is a reversible process.
3257:
2250:
1985:"Isoform Switch of TET1 Regulates DNA Demethylation and Mouse Development"
1694:
1464:
3340:
2299:
1235:
1196:
1026:, allows the stem cell population to be maintained at a constant. As the
1019:
980:
949:
901:
873:
861:
759:
716:
621:
617:
523:
487:
340:
311:
201:
169:
102:
82:
51:
39:
3556:
3104:
1010:
are defined as undifferentiated cells that can differentiate into three
822:
200:, and a large wave of methylation then occurs on days 4.5 to 5.5 in the
3708:
3349:
3152:
2553:
Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, et al. (August 2019).
2174:
Blainey PC, van Oijen AM, Banerjee A, Verdine GL, Xie XS (April 2006).
2115:
Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, et al. (August 2019).
1251:
1231:
775:
573:
565:
399:
391:
315:
into conscious use for a long time. Rats subjected to one instance of
2854:
2456:
1090:
to a myoblast. Another transacting factor that directly transformed a
3249:
2974:
1160:
792:
522:
to initiate demethylation it must first be recruited to a methylated
395:
386:(TDG) recognizes the intermediate bases 5fC and 5caC and excises the
247:(sperm and oocytes) of the next generation. Due to the phenomenon of
209:
189:
185:
181:
161:
134:
94:
86:
63:
3503:
829:. Two cells can be fused together and share nuclear DNA, creating a
3436:"A molecular roadmap of reprogramming somatic cells into iPS cells"
2951:"Biophysical regulation of epigenetic state and cell reprogramming"
1679:"Experience-dependent epigenomic reorganization in the hippocampus"
1357:
1266:
1192:
1156:
1152:
1119:
893:
720:
666:
407:
403:
158:
55:
948:
brought on by the stresses of gene expression change. The use of
750:
The initiation phase is completed through one of three pathways:
502:(8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The
3588:"High-efficiency RNA interference in human embryonic stem cells"
2641:"The Nobel Prize in Physiology or Medicine – 2012 Press Release"
1243:
1239:
1166:
1148:
1143:
1137:
1129:
1115:
1111:
1107:
1083:
965:
922:
914:
889:
885:
881:
662:
658:
654:
604:
531:
443:
411:
3031:"Understanding and Modulating Immunity With Cell Reprogramming"
2282:
van der Kemp PA, Charbonnier JB, Audebert M, Boiteux S (2004).
641:
The first person to successfully demonstrate reprogramming was
172:
in DNA, amounting to about 20 million methylated sites. After
1932:
Melamed P, Yosefzon Y, David C, Tsukerman A, Pnueli L (2018).
1677:
Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD (July 2017).
255:
the primordial germ cells must have their original biparental
117:-specific with changes that presumably define each individual
3492:
2726:"Cellular reprogramming and the rise of rejuvenation biotech"
1934:"Tet Enzymes, Variants, and Differential Effects on Function"
1207:, and cellular transformation for further differentiation.
795:
can reprogram an adult nucleus into an embryonic state after
2233:
Abdou I, Poirier GG, Hendzel MJ, Weinfeld M (January 2015).
1448:"DNA Methylation Reprogramming during Mammalian Development"
101:
is formed, methylation can begin, and with formation of the
940:. Some cells that undergo reprogramming still remain under
799:, so that a new organism can be developed from such cell.
335:
Three molecular stages are required for reprogramming the
239:
DNA methylation dynamic during mouse embryonic development
3029:
Pires CF, Rosa FF, Kurochkin I, Pereira CF (2019-12-11).
470:(CGIs) genome-wide by its CXXC domain that can recognize
1058:, without the use of embryos. It is carried out by the
1062:
of stem-cell associated genes into mature cells using
1038:. In this context, it often refers to the creation of
3387:"In Vivo Cellular Reprogramming: The Next Generation"
1497:
Ladstätter S, Tachibana-Konwalski K (December 2016).
3078:
3076:
2719:
2717:
2715:
2713:
2711:
2709:
192:(at the 16 cell stage), has only a small amount of
3380:
3378:
3376:
840:is used to create a multi nucleated cell called a
766:, epigenetic markers, and other small molecules).
2827:
2825:
2823:
2821:
2819:
2654:
2652:
2650:
2615:Journal of Embryology and Experimental Morphology
105:a wave of methylation then takes place until the
1395:Auclair G, Guibert S, Bender A, Weber M (2014).
802:Reprogramming is distinct from development of a
530:(see figure Initiation of DNA demthylation) and
3481:
3479:
568:in a methylated CpG site, because of a lowered
176:, the paternal chromosome is almost completely
3024:
3022:
2608:
2606:
944:at the beginning of the maturation stage from
742:If the cell is directly reprogrammed from one
426:include at least two isoforms of TET1, one of
97:, which has almost no methylation. After the
3690:
3688:
3322:
3320:
3318:
3020:
3018:
3016:
3014:
3012:
3010:
3008:
3006:
3004:
3002:
2895:
2893:
2891:
2889:
2887:
2885:
2883:
2881:
8:
1824:
1822:
1938:Frontiers in Cell and Developmental Biology
1927:
1925:
964:. One genetic marker is the expression of
307:Brain regions involved in memory formation
3668:
3603:
3511:
3459:
3410:
3385:Srivastava D, DeWitt N (September 2016).
3348:
3298:
3288:
3161:
3151:
3056:
3046:
2982:
2917:
2853:
2799:
2586:
2520:
2510:
2488:
2486:
2484:
2464:
2415:
2366:
2356:
2307:
2258:
2209:
2199:
2150:
2140:
2049:
2000:
1959:
1949:
1905:
1856:
1846:
1802:
1792:
1751:
1702:
1653:
1612:
1571:
1522:
1473:
1463:
1422:
1412:
1358:"Programming of DNA methylation patterns"
133:Timeline of DNA methylation in the mouse
2445:Journal of the American Chemical Society
1636:Wrenzycki C, Niemann H (December 2003).
1002:
855:
821:
779:
481:
353:
302:
278:(DMRS) associated with imprinted genes,
234:
128:
2724:de Magalhães JP, Ocampo A (June 2022).
2075:
2073:
2071:
2069:
1305:
1014:. The ability of self-renewal, through
975:, while epigenetic changes include the
556:, or about 11 minutes in the livers of
2548:
2546:
2544:
2542:
2540:
1732:Neuroscience and Biobehavioral Reviews
1374:10.1146/annurev-biochem-052610-091920
1140:which could aid in differentiation.
985:activation-induced cytidine deaminase
925:. In the later stages of maturation,
486:Initiation of DNA demethylation at a
382:(5fC) and 5-carboxylcytosine (5caC).
7:
3187:Mechanisms of Ageing and Development
2499:Frontiers in Behavioral Neuroscience
1230:accessibility through repression of
30:refers to erasure and remodeling of
1835:Frontiers in Molecular Neuroscience
1781:Frontiers in Molecular Neuroscience
402:(Thy). 5hmU can be cleaved by TDG,
1169:is a transcription factor used in
715:activity is reactivated to extend
372:methylcytosine dioxygenases (TETs)
121:and last stably over a long time.
14:
2643:. Nobel Media AB. 8 October 2012.
860:Defined factors. The addition of
729:mesenchymal–epithelial transition
276:differentially methylated regions
1356:Cedar H, Bergman Y (July 2012).
1046:. This allows the production of
1042:from mature cells such as adult
69:After fertilization in mammals,
1829:Bayraktar G, Kreutz MR (2018).
1775:Bayraktar G, Kreutz MR (2018).
1744:10.1016/j.neubiorev.2005.06.005
1642:Reproductive Biomedicine Online
921:, and Esrrb, followed later by
600:early growth response protein 1
1086:was expressed and converted a
1040:induced pluripotent stem cells
1028:induced pluripotent stem cells
671:induced pluripotent stem cells
141:; blue: male germ line; grey:
58:. In addition, almost 10% of
1:
2900:David L, Polo JM (May 2014).
2745:10.1016/j.tibtech.2022.01.011
2094:10.1016/j.cellsig.2016.05.021
1655:10.1016/s1472-6483(10)62087-1
1614:10.1095/biolreprod.103.017293
1446:Zeng Y, Chen T (March 2019).
1362:Annual Review of Biochemistry
1124:induced pluripotent stem cell
797:somatic cell nuclear transfer
785:Somatic Cell Nuclear Transfer
770:Somatic cell nuclear transfer
579:(MCF-10A) were treated with
212:segregate from the remaining
3290:10.1371/journal.pgen.1000170
2002:10.1016/j.molcel.2016.10.030
1898:10.1016/j.celrep.2015.12.044
1238:. NANOG aids recruitment of
462:do not specifically bind to
317:contextual fear conditioning
3605:10.1634/stemcells.2004-0252
3486:Rizzino A (December 2009).
2493:Duclot F, Kabbaj M (2017).
1226:. NANOG works by promoting
564:preferentially occurs at a
500:8-hydroxy-2'-deoxyguanosine
3771:
3661:10.1038/s41467-019-09041-z
3452:10.1016/j.cell.2012.11.039
3403:10.1016/j.cell.2016.08.055
2846:10.1016/j.cell.2007.11.019
2792:10.1038/stemcells.2007.124
2684:10.1016/j.cell.2006.07.024
2579:10.1038/s41467-019-11905-3
2142:10.1038/s41467-019-11905-3
1515:10.1016/j.cell.2016.11.009
1224:cell determination factors
773:
18:
3199:10.1016/j.mad.2006.01.018
2919:10.1016/j.scr.2014.03.007
2902:"Phases of reprogramming"
1414:10.1186/s13059-014-0545-5
1279:related to cell culture.
1187:histone acetyltransferase
454:Recruitment of TET to DNA
325:differentially methylated
323:neurons were found to be
3048:10.3389/fimmu.2019.02809
2512:10.3389/fnbeh.2017.00035
1951:10.3389/fcell.2018.00022
1848:10.3389/fnmol.2018.00169
1794:10.3389/fnmol.2018.00169
1726:Kim JJ, Jung MW (2006).
1250:, while also recruiting
1054:, such as research into
614:medial prefrontal cortex
560:mice. DNA oxidation by
349:Base excision DNA repair
3035:Frontiers in Immunology
2733:Trends in Biotechnology
2358:10.1073/pnas.0406048101
2201:10.1073/pnas.0509723103
1601:Biology of Reproduction
1327:10.1126/science.1063443
999:In cell culture systems
731:(MET), and the loss of
681:Phases of reprogramming
647:Nobel Prize in Medicine
562:reactive oxygen species
384:Thymine-DNA glycosylase
376:5-hydroxymethylcytosine
360:5-hydroxymethylcytosine
208:(PGC) in the implanted
2408:10.1093/nar/29.10.2117
2396:Nucleic Acids Research
2288:Nucleic Acids Research
2239:Nucleic Acids Research
2042:10.1038/emboj.2012.357
1564:10.1098/rstb.2011.0330
1216:Homeobox protein NANOG
1031:
919:Homeobox protein NANOG
898:Homeobox protein NANOG
869:
834:
810:with the tadpoles and
788:
758:, or defined factors (
725:Homeobox protein NANOG
675:Homeobox protein NANOG
543:Oxoguanine glycosylase
515:
430:and three isoforms of
367:
308:
240:
154:
3641:Nature Communications
3140:Pulmonary Circulation
2780:Pulmonary Circulation
2559:Nature Communications
2121:Nature Communications
1695:10.1101/lm.045112.117
1683:Learning & Memory
1465:10.3390/genes10040257
1252:Brahma-related gene-1
1074:Transcription factors
1036:transcription factors
1006:
993:DNA methyltransferase
859:
825:
783:
727:, while undergoing a
485:
357:
306:
238:
206:primordial germ cells
147:primordial germ cells
132:
125:Embryonic development
3341:10.1038/leu.2015.294
1509:(7): 1774–1787.e13.
1246:, and Esrrb used in
1195:is also known as an
1134:embryonic stem cells
931:transcription factor
878:transcription factor
866:transcription factor
848:cell reprogramming.
764:transcription factor
610:immediate early gene
570:ionization potential
504:base excision repair
436:alternative promoter
422:The isoforms of the
272:base excision repair
21:computer programming
3653:2019NatCo..10.1109H
3557:10.1038/nature05953
3549:2007Natur.448..445D
3242:1997Natur.385..810W
3105:10.1038/nature04955
3097:2006Natur.441.1061H
3091:(7097): 1061–1067.
2967:2013NatMa..12.1154D
2571:2019NatCo..10.3892S
2349:2004PNAS..10113738L
2343:(38): 13738–13743.
2251:10.1093/nar/gku1307
2192:2006PNAS..103.5752B
2133:2019NatCo..10.3892S
2082:Cellular Signalling
1321:(5532): 1089–1093.
1056:stem cell therapies
1052:biomedical research
299:Learning and Memory
3755:Induced stem cells
3709:10.1038/nmeth.3507
3153:10.1038/nrn2022-c1
2906:Stem Cell Research
2300:10.1093/nar/gkh224
1558:(1609): 20110330.
1289:Induced stem cells
1106:The OSKM factors (
1082:(cDNA) coding for
1032:
870:
835:
789:
620:, hippocampus and
516:
477:un-methylated CpGs
368:
309:
249:genomic imprinting
241:
155:
3543:(7152): 445–451.
3236:(6619): 810–813.
2961:(12): 1154–1162.
2457:10.1021/ja411636j
2451:(11): 4223–4235.
2402:(10): 2117–2126.
2186:(15): 5752–5757.
1294:Epigenome editing
1234:markers, such as
1080:complementary DNA
690:, proliferation,
439:additional first
392:apyrimidinic site
268:DNA demethylation
91:DNA demethylation
3762:
3729:
3728:
3692:
3683:
3682:
3672:
3632:
3626:
3625:
3607:
3583:
3577:
3576:
3532:
3526:
3525:
3515:
3483:
3474:
3473:
3463:
3446:(7): 1617–1632.
3431:
3425:
3424:
3414:
3397:(6): 1386–1396.
3382:
3371:
3370:
3352:
3324:
3313:
3312:
3302:
3292:
3268:
3262:
3261:
3250:10.1038/385810a0
3225:
3219:
3218:
3182:
3176:
3175:
3165:
3155:
3131:
3125:
3124:
3080:
3071:
3070:
3060:
3050:
3026:
2997:
2996:
2986:
2975:10.1038/nmat3777
2955:Nature Materials
2946:
2940:
2939:
2921:
2897:
2876:
2875:
2857:
2829:
2814:
2813:
2803:
2771:
2765:
2764:
2730:
2721:
2704:
2703:
2669:
2656:
2645:
2644:
2637:
2631:
2630:
2610:
2601:
2600:
2590:
2550:
2535:
2534:
2524:
2514:
2490:
2479:
2478:
2468:
2436:
2430:
2429:
2419:
2387:
2381:
2380:
2370:
2360:
2328:
2322:
2321:
2311:
2279:
2273:
2272:
2262:
2230:
2224:
2223:
2213:
2203:
2171:
2165:
2164:
2154:
2144:
2112:
2106:
2105:
2088:(9): 1163–1171.
2077:
2064:
2063:
2053:
2030:The EMBO Journal
2021:
2015:
2014:
2004:
1995:(6): 1062–1073.
1980:
1974:
1973:
1963:
1953:
1929:
1920:
1919:
1909:
1877:
1871:
1870:
1860:
1850:
1826:
1817:
1816:
1806:
1796:
1772:
1766:
1765:
1755:
1723:
1717:
1716:
1706:
1674:
1668:
1667:
1657:
1633:
1627:
1626:
1616:
1592:
1586:
1585:
1575:
1543:
1537:
1536:
1526:
1494:
1488:
1487:
1477:
1467:
1443:
1437:
1436:
1426:
1416:
1392:
1386:
1385:
1353:
1347:
1346:
1310:
1222:and suppressing
946:oxidative stress
752:nuclear transfer
577:epithelial cells
496:5-methylcytosine
464:5-methylcytosine
390:resulting in an
380:5-formylcytosine
364:5-formylcytosine
345:5-methylcytosine
331:Molecular stages
280:retrotransposons
60:DNA methylations
3770:
3769:
3765:
3764:
3763:
3761:
3760:
3759:
3735:
3734:
3733:
3732:
3694:
3693:
3686:
3634:
3633:
3629:
3585:
3584:
3580:
3534:
3533:
3529:
3504:10.1002/wsbm.12
3485:
3484:
3477:
3433:
3432:
3428:
3384:
3383:
3374:
3326:
3325:
3316:
3283:(9): e1000170.
3270:
3269:
3265:
3227:
3226:
3222:
3184:
3183:
3179:
3133:
3132:
3128:
3082:
3081:
3074:
3028:
3027:
3000:
2948:
2947:
2943:
2899:
2898:
2879:
2831:
2830:
2817:
2773:
2772:
2768:
2728:
2723:
2722:
2707:
2667:
2663:(August 2006).
2658:
2657:
2648:
2639:
2638:
2634:
2612:
2611:
2604:
2552:
2551:
2538:
2492:
2491:
2482:
2438:
2437:
2433:
2389:
2388:
2384:
2330:
2329:
2325:
2281:
2280:
2276:
2232:
2231:
2227:
2173:
2172:
2168:
2114:
2113:
2109:
2079:
2078:
2067:
2023:
2022:
2018:
1982:
1981:
1977:
1931:
1930:
1923:
1879:
1878:
1874:
1828:
1827:
1820:
1774:
1773:
1769:
1725:
1724:
1720:
1676:
1675:
1671:
1635:
1634:
1630:
1594:
1593:
1589:
1545:
1544:
1540:
1496:
1495:
1491:
1445:
1444:
1440:
1394:
1393:
1389:
1355:
1354:
1350:
1312:
1311:
1307:
1302:
1285:
1276:
1264:
1258:accessibility.
1213:
1175:differentiation
1104:
1076:
1001:
958:
910:
854:
852:Defined factors
820:
812:Dolly the Sheep
804:somatic epitype
778:
772:
709:
692:gene expression
683:
651:Shinya Yamanaka
639:
596:
588:
584:
540:
456:
420:
388:glycosidic bond
333:
301:
287:heterochromatin
257:DNA methylation
194:DNA methylation
151:inner cell mass
127:
77:, and again in
71:DNA methylation
36:DNA methylation
34:marks, such as
24:
17:
12:
11:
5:
3768:
3766:
3758:
3757:
3752:
3747:
3737:
3736:
3731:
3730:
3703:(9): 885–892.
3697:Nature Methods
3684:
3627:
3598:(3): 299–305.
3578:
3527:
3498:(2): 228–236.
3475:
3426:
3372:
3335:(3): 674–682.
3314:
3263:
3220:
3193:(6): 584–589.
3177:
3126:
3072:
2998:
2941:
2912:(3): 754–761.
2877:
2840:(5): 861–872.
2815:
2766:
2739:(6): 639–642.
2705:
2678:(4): 663–676.
2646:
2632:
2602:
2536:
2480:
2431:
2382:
2323:
2294:(2): 570–578.
2274:
2245:(2): 875–892.
2225:
2166:
2107:
2065:
2036:(5): 645–655.
2016:
1989:Molecular Cell
1975:
1921:
1892:(3): 493–505.
1872:
1818:
1767:
1738:(2): 188–202.
1718:
1689:(7): 278–288.
1669:
1648:(6): 649–656.
1628:
1607:(3): 902–914.
1587:
1538:
1489:
1438:
1401:Genome Biology
1387:
1348:
1304:
1303:
1301:
1298:
1297:
1296:
1291:
1284:
1281:
1275:
1272:
1263:
1260:
1212:
1209:
1103:
1100:
1075:
1072:
1018:extending the
1000:
997:
979:extending the
957:
954:
909:
906:
853:
850:
819:
816:
771:
768:
708:
705:
682:
679:
669:) to generate
638:
635:
595:
592:
586:
582:
539:
536:
455:
452:
446:coding for 11
419:
416:
332:
329:
300:
297:
137:. Red: female
126:
123:
15:
13:
10:
9:
6:
4:
3:
2:
3767:
3756:
3753:
3751:
3748:
3746:
3743:
3742:
3740:
3726:
3722:
3718:
3714:
3710:
3706:
3702:
3698:
3691:
3689:
3685:
3680:
3676:
3671:
3666:
3662:
3658:
3654:
3650:
3646:
3642:
3638:
3631:
3628:
3623:
3619:
3615:
3611:
3606:
3601:
3597:
3593:
3589:
3582:
3579:
3574:
3570:
3566:
3562:
3558:
3554:
3550:
3546:
3542:
3538:
3531:
3528:
3523:
3519:
3514:
3509:
3505:
3501:
3497:
3493:
3489:
3482:
3480:
3476:
3471:
3467:
3462:
3457:
3453:
3449:
3445:
3441:
3437:
3430:
3427:
3422:
3418:
3413:
3408:
3404:
3400:
3396:
3392:
3388:
3381:
3379:
3377:
3373:
3368:
3364:
3360:
3356:
3351:
3346:
3342:
3338:
3334:
3330:
3323:
3321:
3319:
3315:
3310:
3306:
3301:
3296:
3291:
3286:
3282:
3278:
3277:PLOS Genetics
3274:
3267:
3264:
3259:
3255:
3251:
3247:
3243:
3239:
3235:
3231:
3224:
3221:
3216:
3212:
3208:
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3200:
3196:
3192:
3188:
3181:
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3169:
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3159:
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3149:
3145:
3141:
3137:
3130:
3127:
3122:
3118:
3114:
3110:
3106:
3102:
3098:
3094:
3090:
3086:
3079:
3077:
3073:
3068:
3064:
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3049:
3044:
3040:
3036:
3032:
3025:
3023:
3021:
3019:
3017:
3015:
3013:
3011:
3009:
3007:
3005:
3003:
2999:
2994:
2990:
2985:
2980:
2976:
2972:
2968:
2964:
2960:
2956:
2952:
2945:
2942:
2937:
2933:
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2925:
2920:
2915:
2911:
2907:
2903:
2896:
2894:
2892:
2890:
2888:
2886:
2884:
2882:
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2873:
2869:
2865:
2861:
2856:
2851:
2847:
2843:
2839:
2835:
2828:
2826:
2824:
2822:
2820:
2816:
2811:
2807:
2802:
2797:
2793:
2789:
2785:
2781:
2777:
2770:
2767:
2762:
2758:
2754:
2750:
2746:
2742:
2738:
2734:
2727:
2720:
2718:
2716:
2714:
2712:
2710:
2706:
2701:
2697:
2693:
2689:
2685:
2681:
2677:
2673:
2666:
2662:
2659:Takahashi K,
2655:
2653:
2651:
2647:
2642:
2636:
2633:
2628:
2624:
2620:
2616:
2609:
2607:
2603:
2598:
2594:
2589:
2584:
2580:
2576:
2572:
2568:
2564:
2560:
2556:
2549:
2547:
2545:
2543:
2541:
2537:
2532:
2528:
2523:
2518:
2513:
2508:
2504:
2500:
2496:
2489:
2487:
2485:
2481:
2476:
2472:
2467:
2462:
2458:
2454:
2450:
2446:
2442:
2435:
2432:
2427:
2423:
2418:
2413:
2409:
2405:
2401:
2397:
2393:
2386:
2383:
2378:
2374:
2369:
2364:
2359:
2354:
2350:
2346:
2342:
2338:
2334:
2327:
2324:
2319:
2315:
2310:
2305:
2301:
2297:
2293:
2289:
2285:
2278:
2275:
2270:
2266:
2261:
2256:
2252:
2248:
2244:
2240:
2236:
2229:
2226:
2221:
2217:
2212:
2207:
2202:
2197:
2193:
2189:
2185:
2181:
2177:
2170:
2167:
2162:
2158:
2153:
2148:
2143:
2138:
2134:
2130:
2126:
2122:
2118:
2111:
2108:
2103:
2099:
2095:
2091:
2087:
2083:
2076:
2074:
2072:
2070:
2066:
2061:
2057:
2052:
2047:
2043:
2039:
2035:
2031:
2027:
2020:
2017:
2012:
2008:
2003:
1998:
1994:
1990:
1986:
1979:
1976:
1971:
1967:
1962:
1957:
1952:
1947:
1943:
1939:
1935:
1928:
1926:
1922:
1917:
1913:
1908:
1903:
1899:
1895:
1891:
1887:
1883:
1876:
1873:
1868:
1864:
1859:
1854:
1849:
1844:
1840:
1836:
1832:
1825:
1823:
1819:
1814:
1810:
1805:
1800:
1795:
1790:
1786:
1782:
1778:
1771:
1768:
1763:
1759:
1754:
1749:
1745:
1741:
1737:
1733:
1729:
1722:
1719:
1714:
1710:
1705:
1700:
1696:
1692:
1688:
1684:
1680:
1673:
1670:
1665:
1661:
1656:
1651:
1647:
1643:
1639:
1632:
1629:
1624:
1620:
1615:
1610:
1606:
1602:
1598:
1591:
1588:
1583:
1579:
1574:
1569:
1565:
1561:
1557:
1553:
1549:
1542:
1539:
1534:
1530:
1525:
1520:
1516:
1512:
1508:
1504:
1500:
1493:
1490:
1485:
1481:
1476:
1471:
1466:
1461:
1457:
1453:
1449:
1442:
1439:
1434:
1430:
1425:
1420:
1415:
1410:
1406:
1402:
1398:
1391:
1388:
1383:
1379:
1375:
1371:
1367:
1363:
1359:
1352:
1349:
1344:
1340:
1336:
1332:
1328:
1324:
1320:
1316:
1309:
1306:
1299:
1295:
1292:
1290:
1287:
1286:
1282:
1280:
1273:
1271:
1268:
1261:
1259:
1257:
1253:
1249:
1248:transcription
1245:
1241:
1237:
1233:
1229:
1225:
1221:
1217:
1210:
1208:
1206:
1203:progression,
1202:
1198:
1194:
1190:
1188:
1184:
1180:
1176:
1172:
1171:proliferation
1168:
1164:
1162:
1158:
1154:
1150:
1145:
1141:
1139:
1135:
1131:
1127:
1125:
1121:
1117:
1113:
1109:
1101:
1099:
1097:
1093:
1092:lymphoid cell
1089:
1085:
1081:
1073:
1071:
1069:
1065:
1064:viral vectors
1061:
1057:
1053:
1049:
1045:
1041:
1037:
1029:
1025:
1021:
1017:
1013:
1009:
1005:
998:
996:
994:
990:
986:
982:
978:
974:
971:
967:
963:
956:Stabilization
955:
953:
951:
947:
943:
939:
934:
932:
928:
924:
920:
916:
907:
905:
903:
899:
895:
891:
887:
883:
879:
875:
867:
863:
858:
851:
849:
847:
843:
839:
832:
828:
824:
817:
815:
813:
809:
805:
800:
798:
794:
786:
782:
777:
769:
767:
765:
761:
757:
753:
748:
745:
740:
738:
734:
730:
726:
722:
718:
714:
706:
704:
701:
697:
693:
689:
680:
678:
676:
672:
668:
664:
660:
656:
652:
648:
644:
636:
634:
631:
627:
623:
619:
615:
611:
607:
606:
601:
593:
591:
589:
578:
575:
571:
567:
563:
559:
555:
552:
548:
544:
537:
535:
533:
529:
525:
521:
513:
509:
505:
501:
497:
493:
489:
484:
480:
478:
473:
472:un-methylated
469:
465:
461:
453:
451:
449:
445:
442:
437:
433:
429:
425:
417:
415:
413:
409:
405:
401:
397:
393:
389:
385:
381:
377:
373:
365:
361:
356:
352:
350:
346:
342:
338:
337:DNA methylome
330:
328:
326:
322:
318:
313:
305:
298:
296:
294:
290:
288:
285:
281:
277:
273:
269:
265:
260:
258:
254:
253:gametogenesis
250:
246:
237:
233:
231:
227:
223:
222:gonadal ridge
217:
215:
214:somatic cells
211:
207:
203:
199:
195:
191:
187:
183:
179:
175:
174:fertilization
171:
167:
163:
160:
152:
148:
144:
140:
136:
131:
124:
122:
120:
116:
112:
108:
104:
100:
96:
92:
88:
84:
80:
79:gametogenesis
76:
75:embryogenesis
72:
67:
65:
61:
57:
53:
49:
48:fertilization
43:
41:
37:
33:
29:
28:reprogramming
22:
3700:
3696:
3644:
3640:
3630:
3595:
3591:
3581:
3540:
3536:
3530:
3495:
3491:
3443:
3439:
3429:
3394:
3390:
3332:
3328:
3280:
3276:
3266:
3233:
3229:
3223:
3190:
3186:
3180:
3143:
3139:
3129:
3088:
3084:
3038:
3034:
2958:
2954:
2944:
2909:
2905:
2837:
2833:
2783:
2779:
2769:
2736:
2732:
2675:
2671:
2635:
2618:
2614:
2562:
2558:
2502:
2498:
2448:
2444:
2434:
2399:
2395:
2385:
2340:
2336:
2326:
2291:
2287:
2277:
2242:
2238:
2228:
2183:
2179:
2169:
2124:
2120:
2110:
2085:
2081:
2033:
2029:
2019:
1992:
1988:
1978:
1941:
1937:
1889:
1886:Cell Reports
1885:
1875:
1838:
1834:
1784:
1780:
1770:
1735:
1731:
1721:
1686:
1682:
1672:
1645:
1641:
1631:
1604:
1600:
1590:
1555:
1551:
1541:
1506:
1502:
1492:
1455:
1451:
1441:
1404:
1400:
1390:
1365:
1361:
1351:
1318:
1314:
1308:
1277:
1265:
1220:pluripotency
1214:
1191:
1183:somatic cell
1165:
1142:
1128:
1105:
1096:myeloid cell
1077:
1068:retroviruses
1060:transfection
1033:
973:reactivation
970:X chromosome
962:pluripotency
959:
938:pluripotency
935:
911:
871:
846:heterokaryon
842:heterokaryon
836:
831:heterokaryon
801:
790:
749:
744:somatic cell
741:
710:
696:pluripotency
684:
640:
603:
599:
597:
553:
541:
517:
476:
471:
463:
457:
421:
369:
347:. Stage 3:
334:
310:
292:
291:
261:
242:
218:
178:demethylated
156:
145:line; PGCs:
143:somatic cell
107:implantation
68:
44:
27:
26:In biology,
25:
3750:Epigenetics
3647:(1): 1109.
3350:10651/43469
2621:: 622–640.
2565:(1): 3892.
2127:(1): 3892.
1407:(12): 545.
1274:Variability
1254:(BRG1) for
1044:fibroblasts
1024:chromosomes
1012:germ layers
991:(TET), and
989:TET enzymes
838:Cell fusion
827:Cell Fusion
818:Cell fusion
808:John Gurdon
756:cell fusion
643:John Gurdon
494:), forming
468:CpG islands
460:TET enzymes
448:amino acids
424:TET enzymes
321:hippocampus
284:centromeric
264:totipotency
3739:Categories
3592:Stem Cells
3146:(1): 976.
2855:2433/49782
2661:Yamanaka S
1640:. Review.
1458:(4): 257.
1368:: 97–117.
1317:(Review).
1300:References
1201:cell cycle
1189:activity.
1088:fibroblast
1048:stem cells
1016:telomerase
1008:Stem cells
977:telomerase
908:Maturation
774:See also:
737:senescence
713:telomerase
707:Initiation
700:telomerase
688:morphology
649:alongside
630:C-terminal
558:irradiated
551:HeLa cells
520:TET enzyme
441:N-terminal
418:TET family
245:germ cells
230:life cycle
198:blastocyst
166:methylated
164:is 80–90%
157:The mouse
111:germ cells
99:blastocyst
85:to form a
32:epigenetic
2761:246990346
1256:chromatin
1228:chromatin
1205:apoptosis
1179:apoptosis
981:telomeres
942:apoptosis
927:transgene
733:apoptosis
717:telomeres
598:The gene
492:CpG sites
270:involves
170:CpG sites
139:germ line
119:cell type
3717:26237226
3679:30846691
3614:15749924
3565:17597761
3522:20016762
3470:23260147
3421:27610565
3359:26500142
3329:Leukemia
3309:18773085
3207:16513160
3172:32166015
3113:16810240
3067:31921109
3041:: 2809.
2993:24141451
2936:31759309
2928:24735951
2864:18035408
2810:32166015
2753:35190201
2692:16904174
2627:13951335
2597:31467272
2531:28321184
2475:24571128
2426:11353081
2377:15365186
2318:14752045
2269:25539916
2220:16585517
2161:31467272
2102:27251462
2060:23353889
2011:27916660
1970:29556496
1916:26774490
1867:29875631
1813:29875631
1762:16120461
1713:28620075
1664:14748963
1623:12748125
1582:23166394
1533:27916276
1484:30934924
1433:25476147
1382:22404632
1343:17089710
1335:11498579
1283:See also
1236:H3K27me3
1197:oncogene
1066:such as
1020:telomere
950:microRNA
902:microRNA
874:microRNA
862:microRNA
760:microRNA
622:amygdala
618:striatum
608:) is an
554:in vitro
524:CpG site
488:CpG site
341:cytosine
312:Learning
293:In vitro
202:epiblast
103:epiblast
89:, rapid
40:histones
3725:9889991
3670:6406003
3649:Bibcode
3622:1395518
3573:4422771
3545:Bibcode
3513:2794141
3461:3608203
3412:6234007
3300:2527997
3258:9039911
3238:Bibcode
3215:9187848
3163:7052475
3121:4304218
3093:Bibcode
2984:9675045
2963:Bibcode
2872:8531539
2801:7052475
2700:1565219
2588:6715719
2567:Bibcode
2522:5337695
2466:3985951
2345:Bibcode
2260:4333375
2211:1458645
2188:Bibcode
2152:6715719
2129:Bibcode
2051:3590984
1961:5844914
1907:4731272
1858:5975432
1841:: 169.
1804:5975432
1787:: 169.
1753:4342048
1704:5473107
1573:3539359
1524:5161750
1475:6523607
1424:4295324
1315:Science
1232:histone
1147:–
1094:into a
987:(AID),
776:cloning
637:History
574:mammary
566:guanine
506:enzyme
400:thymine
186:enzymes
168:at its
149:; ICM:
64:neurons
3723:
3715:
3677:
3667:
3620:
3612:
3571:
3563:
3537:Nature
3520:
3510:
3468:
3458:
3419:
3409:
3367:508334
3365:
3357:
3307:
3297:
3256:
3230:Nature
3213:
3205:
3170:
3160:
3119:
3111:
3085:Nature
3065:
3058:917620
3055:
2991:
2981:
2934:
2926:
2870:
2862:
2808:
2798:
2759:
2751:
2698:
2690:
2625:
2595:
2585:
2529:
2519:
2505:: 35.
2473:
2463:
2424:
2414:
2375:
2368:518826
2365:
2316:
2309:373348
2306:
2267:
2257:
2218:
2208:
2159:
2149:
2100:
2058:
2048:
2009:
1968:
1958:
1944:: 22.
1914:
1904:
1865:
1855:
1811:
1801:
1760:
1750:
1711:
1701:
1662:
1621:
1580:
1570:
1531:
1521:
1482:
1472:
1431:
1421:
1380:
1341:
1333:
1262:C/EBPα
1181:, and
1161:genome
1155:, and
1118:, and
892:, and
793:oocyte
698:, and
665:, and
626:motifs
547:8-OHdG
518:For a
396:APOBEC
210:embryo
190:morula
182:oocyte
162:genome
135:genome
115:tissue
95:morula
87:zygote
50:of an
3721:S2CID
3618:S2CID
3569:S2CID
3363:S2CID
3211:S2CID
3117:S2CID
2932:S2CID
2868:S2CID
2786:(1).
2757:S2CID
2729:(PDF)
2696:S2CID
2668:(PDF)
2417:55450
1452:Genes
1339:S2CID
1267:CEBPA
1211:NANOG
1193:c-Myc
1157:Sox15
1153:Sox11
1120:c-Myc
894:c-Myc
721:Oct-4
667:c-Myc
410:, or
408:NEIL1
404:SMUG1
159:sperm
56:sperm
54:by a
3713:PMID
3675:PMID
3610:PMID
3561:PMID
3518:PMID
3466:PMID
3440:Cell
3417:PMID
3391:Cell
3355:PMID
3305:PMID
3254:PMID
3203:PMID
3168:PMID
3109:PMID
3063:PMID
2989:PMID
2924:PMID
2860:PMID
2834:Cell
2806:PMID
2749:PMID
2688:PMID
2672:Cell
2623:PMID
2593:PMID
2527:PMID
2471:PMID
2422:PMID
2373:PMID
2314:PMID
2265:PMID
2216:PMID
2157:PMID
2098:PMID
2056:PMID
2007:PMID
1966:PMID
1912:PMID
1863:PMID
1809:PMID
1758:PMID
1709:PMID
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