Dynamic DNA methylation: In the right place at the right time

In the paper

“These findings are supported by the identification of both methyltransferase and demethylase for deposition and removal of 6mA, respectively (60, 61).”

What the sources say

• Supported

  The Discussion states that the authors identified N6AMT1 and ALKBH1 as responsible for the addition and removal of 6mA in human genomic DNA, respectively. This directly supports the part of the citing sentence attributed to this paper. (LLM, conf=0.94)

  cites [60] Xiao C-L, N6-Methyladenine DNA Modification in the Human Genome. Mol. Cell 71, 306– 318.e7 (2018). 30017583 source
• Supported

  The sentence cites two sources for two enzymes; this paper supports the demethylase portion. In the section “Alkbh1 encodes a demethylase for N6-mA in ES cells” (page unavailable), the authors report that recombinant ALKBH1 reduces N6-mA and that wild-type Alkbh1 rescues elevated N6-mA in knockout cells. (LLM, conf=0.92)

  cites [61] Wu TP, DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 532, 329– 333 (2016). 27027282 PMC4977844 source

In the paper

“These tissue-type specific DMRs are defined by both lineage specific gain and loss of 5mC during embryogenesis.”

What the sources say

• Not checked yetcites [4] Schultz MD, Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 523, 212– 216 (2015). 26030523 PMC4499021 source

In the paper

“In addition, studies suggest that numerous transcription factors (TFs) can also directly sense the state of cytosine methylation through the modulation of their binding affinity and specificity (26).”

What the sources say

• Not checked yetcites [26] Zhu H, Wang G, Qian J, Transcription factors as readers and effectors of DNA methylation. Nat. Rev. Genet 17, 551– 565 (2016). 27479905 PMC5559737 source

In the paper

“These dynamically methylated CpGs cluster into over 1 million tissue specific differentially methylated regions (DMRs).”

What the sources say

• Not checked yetcites [4] Schultz MD, Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 523, 212– 216 (2015). 26030523 PMC4499021 source
• Not checked yetcites [5] Ziller MJ, Charting a dynamic DNA methylation landscape of the human genome. Nature. 500, 477– 481 (2013). 23925113 PMC3821869 source

In the paper

“The deletion of REST led to increased 5mC at lowly methylated regions normally bound by REST.”

What the sources say

• Not checked yetcites [6] Stadler MB, DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 480, 490– 495 (2011). 22170606 source

In the paper

“Notably, such gain of 5mC can be reversed by re-introducing REST.”

What the sources say

• Not checked yetcites [6] Stadler MB, DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 480, 490– 495 (2011). 22170606 source

In the paper

“and numerous genes are expressed during spermatogenesis despite high level methylation at their promoters (18).”

What the sources say

• Not checked yetcites [18] Hammoud SS, Chromatin and transcription transitions of mammalian adult germline stem cells and spermatogenesis. Cell Stem Cell. 15, 239– 253 (2014). 24835570 source

In the paper

“Promoter H3K4me3, in turn, inhibits the activity of the de novo DNA methyltransferase DNMT3a thus preventing methylation at CGIs (20).”

What the sources say

• Not checked yetcites [20] Guo X, Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature. 517, 640– 644 (2015). 25383530 source

In the paper

“These proteins include components of the H3K4 methyltransferase complex (19).”

What the sources say

• Not checked yetcites [19] Smith ZD, Meissner A, DNA methylation: roles in mammalian development. Nat. Rev. Genet 14, 204– 220 (2013). 23400093 source

In the paper

“For example, global erasure of DNA methylation in primordial germ cells (PGCs) does not lead to widespread transcriptional activation (16, 17)”

What the sources say

• Not checked yetcites [16] Seisenberger S, The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol. Cell 48, 849– 862 (2012). 23219530 PMC3533687 source
• Not checked yetcites [17] Hill PWS, Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte. Nature. 555, 392– 396 (2018). 29513657 PMC5856367 source

In the paper

“The depletion of 5mC at CGIs is, in part, determined by the presence of CpG dinucleotide clusters. that are specifically recognized and protected from methylation by proteins containing a CXXC zinc finger domain (19).”

What the sources say

• Not checked yetcites [19] Smith ZD, Meissner A, DNA methylation: roles in mammalian development. Nat. Rev. Genet 14, 204– 220 (2013). 23400093 source

In the paper

“Intragenic DMRs that stretch for kilobases (large-DMRs) can overlap with tissue defining “signature genes” as well as with predicted super-enhancers, which are clusters of enhancers that function cooperatively (4, 10, 11).”

What the sources say

• Not checked yetcites [4] Schultz MD, Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 523, 212– 216 (2015). 26030523 PMC4499021 source
• Not checked yetcites [10] Luo C, Single Cell Methylomes Identify Neuronal Subtypes and Regulatory Elements in Mammalian Cortex. Science (2017). PMC5570439 28798132 source
• Not checked yetcites [11] Whyte WA, Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 153, 307– 319 (2013). 23582322 PMC3653129 source

In the paper

“Although few analyses have been systematically performed across the lifespan of mammals, existing data suggests that, overall the methylome is stable beyond adolescence (13).”

What the sources say

• Not checked yetcites [13] Lister R, Global epigenomic reconfiguration during mammalian brain development. Science. 341, 1237905 (2013). 23828890 PMC3785061 source

In the paper

“direct comparison of whole genome methylome profiles derived from numerous cell types has revealed that under normal physiological conditions 15%-21% of CpGs vary in methylation status between human tissues (4, 5).”

What the sources say

• Not checked yetcites [4] Schultz MD, Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 523, 212– 216 (2015). 26030523 PMC4499021 source
• Not checked yetcites [5] Ziller MJ, Charting a dynamic DNA methylation landscape of the human genome. Nature. 500, 477– 481 (2013). 23925113 PMC3821869 source

In the paper

“5mC readers including proteins containing a methyl-CpG-binding domain such as MECP2 or MBD proteins can recognize 5mC and recruit co-regulators to methylated DNA (25).”

What the sources say

• Not checked yetcites [25] Du Q, Luu P-L, Stirzaker C, Clark SJ, Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics. 7, 1051– 1073 (2015). 25927341 source

In the paper

“This model has been supported by experiments in mouse embryonic stem cell (mESC) using insulator protein CCCTC-binding factor (CTCF) and a transcriptional repressor of neural genes - RE1-Silencing Transcription factor (REST) (6).”

What the sources say

• Not checked yetcites [6] Stadler MB, DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 480, 490– 495 (2011). 22170606 source

In the paper

“In contrast, aberrant CGI hypermethylation is commonly observed in cancers (2).”

What the sources say

• Not checked yetcites [2] Jones PA, Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet 13, 484– 492 (2012). 22641018 source

In the paper

“In most somatic tissues, the majority (>80%) of CpGs in the genome are methylated, with the exception of CGIs, and other gene regulatory sequences that show reduced 5mC levels (3).”

What the sources say

• Not checked yetcites [3] Lister R, Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 462, 315– 322 (2009). 19829295 PMC2857523 source

In the paper

“Beyond CXXC containing proteins, the depletion of 5mC at CGIs is also dependent on the binding of other specific TFs (19).”

What the sources say

• Not checked yetcites [19] Smith ZD, Meissner A, DNA methylation: roles in mammalian development. Nat. Rev. Genet 14, 204– 220 (2013). 23400093 source

In the paper

“Sequential waves of gain and loss of 5mC in late-fetal to early postnatal development contribute to the majority of 5mC diversity found in differentiated tissues.”

In the paper

“The development of high-throughput assays for TF-DNA interaction has identified many transcription factors with binding specificity altered by the presence of 5mC in recognition sequences (26).”

What the sources say

• Not checked yetcites [26] Zhu H, Wang G, Qian J, Transcription factors as readers and effectors of DNA methylation. Nat. Rev. Genet 17, 551– 565 (2016). 27479905 PMC5559737 source

In the paper

“Although in vitro studies reveal that the majority of TF-DNA interaction can be modulated by 5mC, it is still uncertain how broadly this mechanism contributes to in vivo gene regulatory programs.”

In the paper

“A protein microarray study that interrogated more than 1,500 TFs found over 40 TFs that are able to bind methylated motifs (27).”

What the sources say

• Not checked yetcites [27] Hu S, DNA methylation presents distinct binding sites for human transcription factors. Elife. 2, e00726 (2013). 24015356 PMC3762332 source

In the paper

“MECP2 and 5mCA dependent repression is particularly critical for long genes (with a length greater than 100kb), many of which have neuronal functions (39).”

What the sources say

• Not checked yetcites [39] Gabel HW, Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature. 522, 89– 93 (2015). 25762136 PMC4480648 source

In the paper

“This selective 5mC sensitivity can be explained by the different biophysical property of CTCF’s 11 zinc fingers leading to its sensitivity to specific cytosine within its binding motif being methylated (31).”

What the sources say

• Not checked yetcites [31] Hashimoto H, Structural Basis for the Versatile and Methylation-Dependent Binding of CTCF to DNA. Mol. Cell 66, 711– 720.e3 (2017). 28529057 PMC5542067 source

In the paper

“The interaction between DNMT3B and H3K36me leads to greater levels of intragenic 5mC for active genes in mESC (32).”

What the sources say

• Not checked yetcites [32] Baubec T, Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 520, 243– 247 (2015). 25607372 source

In the paper

“Intriguingly, 5mC only affects CTCF binding at a specific subset of recognition sequences (30).”

What the sources say

• Not checked yetcites [30] Maurano MT, Role of DNA Methylation in Modulating Transcription Factor Occupancy. Cell Rep. 12, 1184– 1195 (2015). 26257180 source

In the paper

“Independent studies have reported that MECP2 binds to both 5mCA and 5mCG sites with high affinity (37, 39, 40).”

What the sources say

• Not checked yetcites [37] Guo JU, Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat. Neurosci 17, 215– 222 (2014). 24362762 PMC3970219 source
• Not checked yetcites [39] Gabel HW, Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature. 522, 89– 93 (2015). 25762136 PMC4480648 source
• Not checked yetcites [40] Mellén M, Ayata P, Heintz N, 5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes. Proc. Natl. Acad. Sci. U. S. A 114, E7812– E7821 (2017). 28847947 PMC5604027 source

In the paper

“These studies unexpectedly uncovered that certain interactions between TFs and low affinity binding sites can be enhanced by the presence of 5mC.”

What the sources say

• Not checked yetcites [28] Yin Y, Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 356 (2017), doi: 10.1126/science.aaj2239. PMC8009048 28473536 source

In the paper

“In neurons, intragenic 5mCH quantitatively modulates gene expression by interacting with MECP2 and recruiting NCoR corepressor complex to chromatin (37–40).”

What the sources say

• Not checked yetcites [37] Guo JU, Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat. Neurosci 17, 215– 222 (2014). 24362762 PMC3970219 source
• Not checked yetcites [38] Chen L, MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc. Natl. Acad. Sci. U. S. A 112, 5509– 5514 (2015). 25870282 PMC4418849 source
• Not checked yetcites [39] Gabel HW, Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature. 522, 89– 93 (2015). 25762136 PMC4480648 source
• Not checked yetcites [40] Mellén M, Ayata P, Heintz N, 5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes. Proc. Natl. Acad. Sci. U. S. A 114, E7812– E7821 (2017). 28847947 PMC5604027 source

In the paper

“Human embryonic stem cells (hESC) and mammalian brain tissues contain abundant non-CG methylation (5mCH, where H equals A, C or T) although the underlying three-base DNA sequence context (5mCAG vs. 5mCAC, respectively) is distinct (3, 13).”

What the sources say

• Not checked yetcites [3] Lister R, Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 462, 315– 322 (2009). 19829295 PMC2857523 source
• Not checked yetcites [13] Lister R, Global epigenomic reconfiguration during mammalian brain development. Science. 341, 1237905 (2013). 23828890 PMC3785061 source

In the paper

“CA sites are the most frequently methylated non-CG sites (13).”

What the sources say

• Not checked yetcites [13] Lister R, Global epigenomic reconfiguration during mammalian brain development. Science. 341, 1237905 (2013). 23828890 PMC3785061 source

In the paper

“In PMD associated tissues such cultured fibroblasts, genes located in PMDs are both lowly expressed and methylated (3).”

What the sources say

• Not checked yetcites [3] Lister R, Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 462, 315– 322 (2009). 19829295 PMC2857523 source

In the paper

“However, this correlation appears to be tissue specific.”

In the paper

“Studies with mESC and a heterologous yeast system found that the establishment of intragenic 5mC is a controlled process carried out by de novo DNA methyltransferase DNMT3B and co-transcriptionally regulated histone modification H3K36me (32, 33).”

What the sources say

• Not checked yetcites [32] Baubec T, Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 520, 243– 247 (2015). 25607372 source
• Not checked yetcites [33] Morselli M, In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse. Elife. 4, e06205 (2015). 25848745 PMC4412109 source

In the paper

“Although in vitro studies reveal that the majority of TF-DNA interaction can be modulated by 5mC, it is still uncertain how broadly this mechanism contributes to in vivo gene regulatory programs.”

In the paper

“Indeed, for certain tissue types, active genes are more methylated than repressed genes.”

What the sources say

• Not checked yetcites [2] Jones PA, Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet 13, 484– 492 (2012). 22641018 source

In the paper

“Although promoter 5mC shows a negative correlation with transcription, early studies of intragenic 5mC function posited the opposite finding (2).”

What the sources say

• Not checked yetcites [2] Jones PA, Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet 13, 484– 492 (2012). 22641018 source

In the paper

“Analysis of the whole genome methylomes of 39 primary tumors in mouse and human shows a pronounced loss of methylation at nuclear lamina associated partially methylated domains (PMDs) located in late replicating parts of the genome (44).”

What the sources say

• Not checked yetcites [44] Zhou W, DNA methylation loss in late-replicating domains is linked to mitotic cell division. Nat. Genet 50, 591– 602 (2018). 29610480 PMC5893360 source

In the paper

“Functional analyses of 5mC have traditionally relied on pharmacological or genetic perturbations that affect 5mC levels genome-wide (30, 32).”

What the sources say

• Not checked yetcites [30] Maurano MT, Role of DNA Methylation in Modulating Transcription Factor Occupancy. Cell Rep. 12, 1184– 1195 (2015). 26257180 source
• Not checked yetcites [32] Baubec T, Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 520, 243– 247 (2015). 25607372 source

In the paper

“Local amplification of regulator concentration through protein (SunTag) or RNA scaffolding (e.g. Casilio) has been incorporated into epigenetic editing to enhance the on/off target ratio (Fig. 3).”

What the sources say

• Not checked yetcites [58] Pflueger C, A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs. Genome Res. (2018), doi: 10.1101/gr.233049.117. PMC6071642 29907613 source

In the paper

“Although computational approaches for tissue deconvolution are improving (48), bulk tissue analyses cannot easily distinguish molecular signatures contributed by distinct cell populations.”

What the sources say

• Not checked yetcites [48] Jaffe AE, Irizarry RA, Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol. 15, R31 (2014). 24495553 PMC4053810 source

In the paper

“dCas9-TET and dCas9-DNMT3a fusions have been shown to induce effective remodeling of 5mC (Fig. 3) (56).”

What the sources say

• Not checked yetcites [56] Liu XS, Editing DNA Methylation in the Mammalian Genome. Cell. 167, 233– 247.e17 (2016). 27662091 PMC5062609 source

In the paper

“Despite global DNA hypomethylation, a limited number of genomic loci gain DNA methylation during aging and in cancer.”

What the sources say

• Not checked yetcites [47] Schlesinger Y, Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet 39, 232– 236 (2007). 17200670 source

In the paper

“Unlike single cell RNA-seq which captures transcriptomic information, single nuclei methylome data allowed prediction of cell-type specific regulatory elements with 5mC signatures.”

In the paper

“Modern genome engineering tools have opened up the possibility for a more precise site specific intervention that would potentially avoid pleiotropic effects of global 5mC disruption (55).”

What the sources say

• Not checked yetcites [55] Pulecio J, Verma N, Mejía-Ramírez E, Huangfu D, Raya A, CRISPR/Cas9-Based Engineering of the Epigenome. Cell Stem Cell. 21, 431– 447 (2017). 28985525 PMC6205890 source

In the paper

“This is also supported by the abundance of 5hmC in the brain (up to 20% of 5mCG+5hmCG) (13, 40).”

What the sources say

• Not checked yetcites [13] Lister R, Global epigenomic reconfiguration during mammalian brain development. Science. 341, 1237905 (2013). 23828890 PMC3785061 source
• Not checked yetcites [40] Mellén M, Ayata P, Heintz N, 5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes. Proc. Natl. Acad. Sci. U. S. A 114, E7812– E7821 (2017). 28847947 PMC5604027 source

In the paper

“Building upon single-cell methylome methods, single cell multi-omics approaches have been developed that are capable of analyzing both the transcriptomic and epigenomic profiles from a single cell (49).”

What the sources say

• Not checked yetcites [49] Kelsey G, Stegle O, Reik W, Single-cell epigenomics: Recording the past and predicting the future. Science. 358, 69– 75 (2017). 28983045 source

In the paper

“The similarity between tumor and placenta methylomes suggests that tumorigenesis may represent a latent developmental epigenomic program.”

What the sources say

• Not checked yetcites [46] Smith ZD, Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature. 549, 543– 547 (2017). 28959968 PMC5789792 source

In the paper

“Datasets containing thousands of single-cell methylomes, such as neuron classification in the human and mouse frontal cortices, have been generated with a well-based nuclei collection method, snmC-seq, or a combinatorial indexing-based method, sci-MET (10, 50).”

What the sources say

• Not checked yetcites [10] Luo C, Single Cell Methylomes Identify Neuronal Subtypes and Regulatory Elements in Mammalian Cortex. Science (2017). PMC5570439 28798132 source
• Not checked yetcites [50] Mulqueen RM, Highly scalable generation of DNA methylation profiles in single cells. Nat. Biotechnol 36, 428– 431 (2018). 29644997 PMC5938134 source

In the paper

“Although sequencing-based approaches have only found 5hmC in CG dinucleotides in mESC and brain cortical tissue (24), 5hmCH accounted for 38% of 5mCH+5hmCH in cerebellar granule cells, suggesting that 5mCH is also targeted for TET mediated methylation turnover (40).”

What the sources say

• Not checked yetcites [24] Wu H, Zhang Y, Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell. 156, 45– 68 (2014). 24439369 PMC3938284 source

In the paper

“The situation is, however, different under pathological conditions where the global loss of DNA methylation is often associated with an aberrant transcriptional outcome.”

In the paper

“In addition to sequencing-based single-cell methylome strategies, a fluorescent in vivo reporter of genomic methylation (RGM) enables microscopic examination of the 5mC status at a single genomic locus with cellular resolution (53).”

What the sources say

• Not checked yetcites [53] Stelzer Y, Shivalila CS, Soldner F, Markoulaki S, Jaenisch R, Tracing dynamic changes of DNA methylation at single-cell resolution. Cell. 163, 218– 229 (2015). 26406378 PMC4583717 source

In the paper

“Although single-cell methods are just starting to be applied to analyzing 5mC functions, studies have already identified 5mC heterogeneity both across or within cell types, providing information that cannot be accessed with bulk level analyses.”

In the paper

“In an alternative strategy, the fluorescent protein gene reporter can be directly inserted into the methylation sensitive locus which provides a direct readout of the methylation status in living cells or a whole animal (54).”

What the sources say

• Not checked yetcites [54] Van de Pette M, Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults. Cell Rep. 18, 1090– 1099 (2017). 28147266 PMC5300902 source

In the paper

“For example, a recent methylation editing study demonstrating that deposition of 5mC at thousands of gene promoters led to only moderate transcriptional alterations (65, 66).”

What the sources say

• Not checked yetcites [65] Ford EE, Grimmer MR, Stolzenburg S, Bogdanovic O, Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation. bioRxiv (2017) (available at http://www.biorxiv.org/content/early/2017/08/17/170506.abstract). source
• Not checked yetcites [66] Korthauer K, Irizarry RA, Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation. bioRxiv (2018) (available at https://www.biorxiv.org/content/early/2018/08/01/381145.abstract). source

In the paper

“This scaffold allows multiple copies of epigenetic effectors (e.g. DNMT3A catalytic domain) to be tethered to a genomic site, providing more robust on-target modulation and reduced non-specific effects (58).”

What the sources say

• Not checked yetcites [58] Pflueger C, A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs. Genome Res. (2018), doi: 10.1101/gr.233049.117. PMC6071642 29907613 source

In the paper

“Interestingly, the genome-wide distribution of 6mA is species-specific with lack of a conserved pattern across the eukaryotic species analyzed to date (59).”

What the sources say

• Not checked yetcites [59] Luo G-Z, He C, DNA N6-methyladenine in metazoans: functional epigenetic mark or bystander ? Nat. Struct. Mol. Biol 24, 503– 506 (2017). 28586322 source

In the paper

“Reported difference in 6mA distribution between mouse and human may represent tissue specific patterns rather than species differences, since the tissues used for the mouse and human studies were unique to each species (mESC and blood DNA, respectively (60, 61)).”

What the sources say

• Not checked yetcites [60] Xiao C-L, N6-Methyladenine DNA Modification in the Human Genome. Mol. Cell 71, 306– 318.e7 (2018). 30017583 source
• Not checked yetcites [61] Wu TP, DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 532, 329– 333 (2016). 27027282 PMC4977844 source

In the paper

“Animal models, such as mouse fear conditioning, suggests a role for 5mC in regulating learning and memory (62).”

What the sources say

• Not checked yetcites [62] Day JJ, Kennedy AJ, Sweatt JD, DNA methylation and its implications and accessibility for neuropsychiatric therapeutics. Annu. Rev. Pharmacol. Toxicol 55, 591– 611 (2015). 25340930 PMC4768530 source

In the paper

“Compelling multimodal evidence has been presented for the existence of 6mA in mouse and human genomes.”

What the sources say

• Not checked yetcites [59] Luo G-Z, He C, DNA N6-methyladenine in metazoans: functional epigenetic mark or bystander ? Nat. Struct. Mol. Biol 24, 503– 506 (2017). 28586322 source

In the paper

“In mitotically inactive mammalian tissues, moderate changes in 5mC dynamics likely reflect cellular heterogeneity either across cell types or within a cell type.”