Epigenetic regulation of Dnmt3a and Arc gene expression after electroconvulsive stimulation in the rat

Dyrvig, Mads; Gøtzsche, Casper René; Woldbye, David P. D.; Lichota, Jacek

doi:10.1016/j.mcn.2015.06.011

Cited by 21 publications

(16 citation statements)

References 44 publications

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“…Both inhibitors impose global DNA hypomethylation and DNA damage in cells although they can also exert drug-specific actions on cell viability, protein synthesis, the cell cycle and gene expression [57, 58]. In tumor cell lines, in vitro exposures to 5-azaCdR reduced dnmt1 and dnmt3b mRNA expression and protein levels, and to a lesser extent dnmt3a [58–61]. The depletion in Dnmt1 was reported to be proteasome-mediated since it started even earlier than the incorporation of 5-azaCdR into DNA and the formation of aza-Dnmt-DNA adducts [62].…”

Section: Discussionmentioning

confidence: 99%

Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis

et al. 2017

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BackgroundThe identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2′-deoxycytidine) and temperature was evaluated.ResultsFive paralog genes of dnmt3, namely dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb.1 and dnmt3bb.2 and one gene for dnmt1 were identified. Phylogenetic analysis revealed that the dnmt gene family was highly conserved in teleosts and three fish-specific genes, dnmt3aa, dnmt3ba and dnmt3bb.2 have evolved. The spatio-temporal expression patterns of four dnmts (dnmt1, dnmt3aa, dnmt3ab and dnmt3bb.1) were different in early larval stages although all of them reduced expression with the age and were detected in neural organs and dnmt3aa appeared specific to somites. In juveniles, the four dnmt genes were expressed in brain and hematopoietic tissues such as kidney, spleen and gills. Treatment of sole embryos with 5-aza-2′-deoxycytidine down-regulated dntm1 and up-regulated dntm3aa. Moreover, in lecithotrophic larval stages, dnmt3aa and dnmt3ab were temperature sensitive and their expression was higher in larvae incubated at 16 °C relative to 20 °C.ConclusionFive dnmt3 and one dnmt1 paralog were identified in sole and their distinct developmental and tissue-specific expression patterns indicate that they may have different roles during development. The inhibitor 5-aza-2′-deoxycytidine modified the transcript abundance of dntm1 and dntm3aa in embryos, which suggests that a regulatory feedback mechanism exists for these genes. The impact of thermal regime on expression levels of dnmt3aa and dnmt3ab in lecithotrophic larval stages suggests that these paralogs might be involved in thermal programing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-017-0154-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis

et al. 2017

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“…A number of studies reported associations between polymorphisms in the SLC6A4 gene, MDD, and related traits, such as anxiety (Heinz et al, 2005;Munafo, Brown, & Hariri, 2008;Surguladze et al, 2008) and AD treatment response (Manoharan, Shewade, Rajkumar, & Adithan, 2016). Fewer studies investigated the role of the ARC gene, despite it being considered a strong candidate for involvement in MDD and AD response (Dyrvig, Gotzsche, Woldbye, & Lichota, 2015;Li et al, 2015;Molteni, Calabrese, Mancini, Racagni, & Riva, 2008). Indeed, ARC is an early onset gene with an important role in neuroplasticity (Li et al, 2015;Peebles et al, 2010).…”

Section: Overview Of Findingsmentioning

confidence: 99%

The serotonin transporter and the activity regulated cytoskeleton‐associated protein genes in antidepressant response and resistance: 5‐HTTLPR and other variants

Calabrò

Fabbri

Crisafulli

et al. 2018

Human Psychopharmacology

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Objective Previous evidence suggested the involvement of serotonin transporter (SLC6A4) and activity regulated cytoskeleton‐associated protein (ARC) in antidepressant action. This study investigated their role in antidepressant efficacy and treatment‐resistant depression (TRD). Methods Three samples (n total = 648) were investigated to test the association between treatment outcomes (response, remission, symptom improvement, and TRD) and 11 polymorphisms within SLC6A4 and ARC genes. The possible modulating effect of age and gender was considered. Response and remission were also investigated using a fixed‐effects meta‐analysis of the three samples. Results SLC6A4 5‐HTTLPR/rs25531 effects on symptom improvement were modulated by age (better improvement in L/LA carriers in older subjects) and gender (better improvement in L/LA female carriers). SLC6A4 STin2 long alleles were associated with remission and lower risk of TRD. Preliminary evidence of association between ARC rs11167152/rs10110456 and different outcomes was found. Conclusions 5‐HTTLPR/rs25531 effect on antidepressant efficacy was modulated by age, in line with previous literature data. STin2 effect on antidepressant efficacy was in line with previous meta‐analyses. A new possible effect of ARC variants on antidepressant efficacy was observed; however, further studies in larger samples are needed to confirm their role.

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“…Second, hydroxymethylation (hmC) (14) involves enzymatic oxidation of the methyl group base by the ten–eleven translocases (TET1, TET2, TET3) and occurs predominantly in the CG context (15,16). Studies suggest that hmC broadly impacts brain function and neural plasticity (5,17,18). Examples include positive correlations between hmC levels and cerebellar development (5), the association of fear extinction (an important form of reversal learning) to a dramatic genome-wide redistribution of hmC within the infralimbic prefrontal cortex (19) and the memory deficits exhibited by TET1 knockout mice (20).…”

Section: Introductionmentioning

confidence: 99%

Enrichment methods provide a feasible approach to comprehensive and adequately powered investigations of the brain methylome

Chan

Shabalin

Xie

et al. 2017

Nucleic Acids Research

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Methylome-wide association studies are typically performed using microarray technologies that only assay a very small fraction of the CG methylome and entirely miss two forms of methylation that are common in brain and likely of particular relevance for neuroscience and psychiatric disorders. The alternative is to use whole genome bisulfite (WGB) sequencing but this approach is not yet practically feasible with sample sizes required for adequate statistical power. We argue for revisiting methylation enrichment methods that, provided optimal protocols are used, enable comprehensive, adequately powered and cost-effective genome-wide investigations of the brain methylome. To support our claim we use data showing that enrichment methods approximate the sensitivity obtained with WGB methods and with slightly better specificity. However, this performance is achieved at <5% of the reagent costs. Furthermore, because many more samples can be sequenced simultaneously, projects can be completed about 15 times faster. Currently the only viable option available for comprehensive brain methylome studies, enrichment methods may be critical for moving the field forward.

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Epigenetic regulation of Dnmt3a and Arc gene expression after electroconvulsive stimulation in the rat

Cited by 21 publications

References 44 publications

Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis

Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis

The serotonin transporter and the activity regulated cytoskeleton‐associated protein genes in antidepressant response and resistance: 5‐HTTLPR and other variants

Enrichment methods provide a feasible approach to comprehensive and adequately powered investigations of the brain methylome

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