Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice

Goto, Kaoru; Numata, Masayuki; Komura, Jun‐ichiro; Ono, Tetsuya; Bestor, Timothy H.; Kondo, Hisatake

doi:10.1046/j.1432-0436.1994.56120039.x

Cited by 198 publications

(113 citation statements)

References 15 publications

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“…In support of this 'DNMT stasis' hypothesis, the activity and expression of DNMT significantly decreases in differentiated cells and is positively correlated with the proliferative state of cells (Goto et al, 1994;Singer-Sam et al, 1990;Yen et al, 1992). However, DNMT stasis is likely to be absent in the mature brain.…”

Section: Discussionmentioning

confidence: 79%

Persistent overexpression of DNA methyltransferase 1 attenuating GABAergic inhibition in basolateral amygdala accounts for anxiety in rat offspring exposed perinatally to low-dose bisphenol A

Zhou¹,

Chen²,

Fei³

et al. 2013

Journal of Psychiatric Research

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Section: Discussionmentioning

confidence: 79%

Persistent overexpression of DNA methyltransferase 1 attenuating GABAergic inhibition in basolateral amygdala accounts for anxiety in rat offspring exposed perinatally to low-dose bisphenol A

Zhou¹,

Chen²,

Fei³

et al. 2013

Journal of Psychiatric Research

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“…The DNMT isoforms 1, 3A, and 3B are expressed in the adult mammalian CNS (13,44,45). Several studies suggest that the Ras-MEK-ERK signaling pathway, a pathway essential for induction of synaptic plasticity and formation of long term memory (36), regulates expression of DNMT genes in nonneuronal cells (46 -48).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, there are small populations of stem cells in various regions of the brain that have the potential to develop into new neurons (15). Therefore, reports that the adult central nervous system (CNS) possesses relatively high levels of DNMT mRNA and enzyme activity were surprising (5,13,16). Early studies into the function of DNMT in the brain suggested that this enzyme might be involved in DNA repair and neurodegeneration (16 -19).…”

mentioning

confidence: 99%

Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus

Levenson¹,

Roth²,

Lubin³

et al. 2006

Journal of Biological Chemistry

572

449

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DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS. DNA (cytosine-5) methyltransferases (DNMTs)5 are a family of enzymes that catalyze the methylation of cytosine residues (1-5). Many biological processes, including imprinting, differentiation, X-chromosome inactivation, and long term transcriptional regulation, involve cytosine methylation, a covalent modification of DNA (6, 7). Tissue-specific patterns of DNA methylation are established early during development as a consequence of cellular differentiation (8, 9). Expression and activity of DNMT is generally restricted to dividing cells and is very high during early development (5, 10 -13). In most cell types, DNMT expression diminishes greatly once terminal differentiation occurs (5, 10 -14).The mammalian brain consists primarily of postmitotic neurons and glial cells that possess relatively low proliferative potential. In addition, there are small populations of stem cells in various regions of the brain that have the potential to develop into new neurons (15). Therefore, reports that the adult central nervous system (CNS) possesses relatively high levels of DNMT mRNA and enzyme activity were surprising (5, 13, 16). Early studies into the function of DNMT in the brain suggested that this enzyme might be involved in DNA repair and neurodegeneration (16 -19). Important recent studies also have implicated misregulation of DNMT specifically or DNA methylation in general in such cognitive disorders as schizophrenia, Rett syndrome, and Fragile X mental retardation (20 -22).Epigenetics refers to a set of self-perpetuating post-translational modifications of DNA and nuclear proteins that produce lasting alterations in ch...

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“…It has been shown that DNA methyltransferase activity is critical for neuronal cell differentiation induced by nerve growth factor (9). In addition, nonproliferating neurons express high levels of DNA methyltransferase, suggesting it may perform functions other than in DNA replication (10), such as DNA mismatch repair in the adult brain (11). Many genes encoding transcription factors were also up-regulated (e.g., myelin gene expression factor and an estrogen-responsive finger protein), with the notable exception of retinoid X receptor (RXR) alpha, whose expression decreased dramatically (Ϫ26 and Ϫ16-fold at 3 and 6 h, respectively) ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Effects of environmental enrichment on gene expression in the brain

Rampon

Jiang

Dong

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

557

359

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Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice

Cited by 198 publications

References 15 publications

Persistent overexpression of DNA methyltransferase 1 attenuating GABAergic inhibition in basolateral amygdala accounts for anxiety in rat offspring exposed perinatally to low-dose bisphenol A

Persistent overexpression of DNA methyltransferase 1 attenuating GABAergic inhibition in basolateral amygdala accounts for anxiety in rat offspring exposed perinatally to low-dose bisphenol A

Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus

Effects of environmental enrichment on gene expression in the brain

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