Evidence for adenine methylation within the mouse myogenic gene Myo-D1

Kay, Peter; Pereira, Eliana Ternes; Marlow, S.A.; Turbett, Gavin R.; Mitchell, Christopher A.; Jacobsen, P.F.; Holliday, Robin; Papadimitriou, J. M.

doi:10.1016/0378-1119(94)90636-x

Cited by 29 publications

(22 citation statements)

References 21 publications

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“…Pintor-Tore (1987) demonstrated that Dpn I sensitive restriction sites are found within maize zein genes, consistent with the presence of 6-methyladenine. Recently Kay et al (1994) reported that many Taq I sites in the mouse Myo-D1 gene are insensitive to digestion, suggesting that 6-methyladenine is present in this gene. Such observations coupled with these data raise the intriguing possibility that 6-methyladenine might play an in vivo role in eukaryotic gene regulation.…”

Section: Discussionmentioning

confidence: 99%

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Adenine methylation atdam sites increases transient gene expression in plant cells

Graham

Larkin

1995

Transgenic Research

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Escherichia coli encodes two major DNA methylation systems: dam, which produces 6-methyladenine; and dcm, which produces 5-methylcytosine. About 1-2% of adenine and cytosine residues in plasmid DNAs prepared in E. coli are methylated by these systems. Since DNA methylation profoundly influences gene expression in eukaryotes, we were interested in determining whether these bacterially encoded modifications might also effect plant gene expression in experimental systems. We therefore examined the influence of dam and dcm methylation on gene expression from four GUS fusion constructs in transient assays in protoplasts and microprojectile-bombarded whole tissues. In these constructs, GUS expression was driven by promoter regions derived from the Arabidopsis alcohol dehydrogenase (Adh1), maize ubiquitin (Ubi1), rice actin (Act1) and CaMV 35S genes. We show that methyladenine produced by dam methylation increased gene expression from constructs based on the Adh1, Ubi1 and Act1 genes. The increase in gene expression ranged from three-fold for Ubi1 and Adh1 in protoplasts to 50-fold for Act1 in bombarded wheat tissues. Expression of a 35S.GUS construct was, however, insensitive to dam methylation. dcm methylation had little if any effect on transient gene expression for any of these constructs. We provide indirect evidence that the critical sites of adenine methylation lie within sequences from the promoter regions, suggesting that dam methylation increases transcription rate. These results have important experimental implications and also raise the intriguing possibility that methyladenine might play a role in the regulation of gene expression in vivo.

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Section: Discussionmentioning

confidence: 99%

“…0962-8819 9 1995 Chapman & Hall evidence, based on restriction enzyme sensitivities, suggests that 6-methyladenine is found in plant and animal genomic DNAs (Pintor-Toro, 1987;Kay et al, 1994), but there is no indication of any in vivo role this modification might play in eukaryotes.…”

Section: Introductionmentioning

confidence: 97%

Adenine methylation atdam sites increases transient gene expression in plant cells

Graham

Larkin

1995

Transgenic Research

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“…However, indirect evidence obtained using restriction enzymes sensitive to adenine methylation suggests the presence of m6A in the mouse Myo-D1 gene and in the rat type 2 steroid 5a-reductase gene. (11,12) In the case of the rat type 2 steroid 5a-reductase gene, the restriction pattern is correlated to its expression. (12) Interestingly, evidence suggests that m6A does affect the regulation of gene expression in mammalian cells.…”

Section: M6a In Protist Dnamentioning

confidence: 98%

“…1). (10)(11)(12)(13)(14) This review focuses on m6A as the sixth base of DNA and aims to be a source of information and inspiration for the development of new ideas and hypotheses on the possible functions of m6A in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenine: the other methylated base of DNA

et al. 2006

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Contrary to mammalian DNA, which is thought to contain only 5-methylcytosine (m5C), bacterial DNA contains two additional methylated bases, namely N6-methyladenine (m6A), and N4-methylcytosine (m4C). However, if the main function of m5C and m4C in bacteria is protection against restriction enzymes, the roles of m6A are multiple and include, for example, the regulation of virulence and the control of many bacterial DNA functions such as the replication, repair, expression and transposition of DNA. Interestingly, even if adenine methylation is usually considered a bacterial DNA feature, the presence of m6A has been found in protist and plant DNAs. Furthermore, indirect evidence suggests the presence of m6A in mammal DNA, raising the possibility that this base has remained undetected due to the low sensitivity of the analytical methods used. This highlights the importance of considering m6A as the sixth element of DNA.

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“…Researchers have been able to detect other DNA base modifications in the mammalian genome, including 5fC and 5CaC during stem cell differentiation , as well as in response to oxidative stress (causally linked to inflammation) (David et al 2007); and N-6-methyladenine in the regulation of Myo-D1 gene expression (Kay et al 1994). Thus, there is convincing evidence to suggest that DNA modifications are not limited to cytosine in the mammalian genome.…”

Section: Cell-type-and Locus-specific Smrt-sequencingmentioning

confidence: 97%

Tet-mediated DNA hydroxymethylation within the prefrontal cortex as a mechanism for the formation and maintenance of fear-related memory

Li¹

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Anxiety disorders are characterized by a significant impairment in one's ability to inhibit or control their fear in response to cues that remind them of the initiating traumatic event. On the other hand, fear extinction is the gradual reduction in fear response, which occurs through repeated presentation of non-reinforced fear-related cues. Fear extinction is therefore an important evolutionarily conserved behavioural adaptation that is essential for survival. The evidence indicates that the infralimbic region of the medial prefrontal cortex (ILPFC) plays a critical role in the acquisition and maintenance of fear extinction memory; however, the cellular and molecular mechanisms involved in the formation and maintenance of fear extinction memory have not been fully elucidated.Epigenetic mechanisms are critically involved in the regulation of gene expression underlying learning and memory. Dynamic variation in cytosine methylation has emerged as a primary mechanism underlying experience-dependent plasticity in the nervous system and in the formation of fear-related memory. However, cytosine methylation is not the only DNA modification in eukaryotic genome. Recent studies have shown that 5-methylcytosine (5mC) can be oxidized and converted to 5-hydroxymethylaton (5hmC) by the ten-eleven translocation (Tet) family proteins. Moreover, 5hmC has been found to be highly enriched in the adult brain, can be dynamically regulated by neural activity, and accumulates across the lifespan. In this thesis, I build upon the hypothesis that Tet-mediated accumulation of 5hmC may underpin the novel cellular and molecular processes that contribute to fear extinction memory. In support of this hypothesis, I first demonstrate that Tet3 gene expression is associated with neuronal activation in vitro. We next found that the expression of Tet3 mRNA, not Tet1 mRNA, is specifically induced after fear extinction training, in vivo. Interestingly, by blocking fear extinction with the NMDA antagonist, MK-801, we found that learning-induced Tet3 mRNA expression is inhibited. Furthermore, lentiviral-mediated knockdown of Tet3 inhibits the consolidation of fear extinction memory.These data strongly suggest that Tet3 is critical for fear extinction memory.To expand on these findings, we performed high-throughput genome-wide sequencing for 5hmC. This was enabled by sequencing samples derived from the infralimibic prefrontal cortex (ILPFC) of mice. We developed a novel protocol that allows one to profile the genome-wide landscape of 5hmC within the ILPFC of individual mice using low input DNA.By adopting this protocol, we mapped out the accumulation of 5hmC across the genome in the ILPFC following fear acquisition and fear extinction. We have found that, upon 2 behavioural training, there is a dramatic redistribution of 5hmC in response to learning.Moreover, by comparing the genome-wide data between fear conditioned and fear extinction-trained mice, we identified 233 unique genomic loci that exhibit accumulation of 5hmC after extinction tra...

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Evidence for adenine methylation within the mouse myogenic gene Myo-D1

Cited by 29 publications

References 21 publications

Adenine methylation atdam sites increases transient gene expression in plant cells

Adenine methylation atdam sites increases transient gene expression in plant cells

N6-methyladenine: the other methylated base of DNA

Tet-mediated DNA hydroxymethylation within the prefrontal cortex as a mechanism for the formation and maintenance of fear-related memory

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