The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes

Weaver, Ian C.G.; D’Alessio, Ana C.; Brown, Shelley E.; Hellstrom, Ian C.; Dymov, Sergiy; Sharma, Shakti; Szyf, Moshe; Meaney, Michael J.

doi:10.1523/jneurosci.4164-06.2007

Cited by 464 publications

(446 citation statements)

References 40 publications

(75 reference statements)

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“…Pup LG increases hippocampal NGFI-A expression and chromatin immunoprecipitation (ChIP) assays, which permit quantification of protein interactions with specific DNA sequences, with hippocampal samples reveal increased NGFI-A association with the exon 1 7 promoter in pups of High compared with Low LG mothers [45]. Co-transfection studies reveal NGFI-A-induced activation of transcription through the exon 1 7 promoter [45]. The effect of NGFI-A is eliminated by a site-directed mutation within the NGFI-A response element of the exon 1 7 promoter [45] such that the physical interaction of NGFI-A with its response element triggers transcriptional activation.…”

Section: Molecular Transduction Of Parental Signalsmentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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a b s t r a c tParental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands. In this review we explore recent studies from the field of 'environmental epigenetics' that suggest that (1) DNA methylation states are far more variable than once thought and that, at least within specific regions of the genome, there is evidence for both demethylation and remethylation in post-mitotic cells and (2) that such remodeling of DNA methylation can occur in response to environmentally-driven, intracellular signaling pathways. Thus, studies of variation in mother-offspring interactions in rodents suggest that parental signals operate during pre-and/ or post-natal life to influence the DNA methylation state at specific regions of the genome leading to sustained changes in gene expression and function. We suggest that DNA methylation is a candidate mechanism for parental effects on phenotypic variation.

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Section: Molecular Transduction Of Parental Signalsmentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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“…CBP is also an acetyl transferase, which acetylates histones [Ogryzko et al, 1996]. We will discuss below the possible involvement of CBP in mediating demethylation in response to maternal care [Weaver et al, 2007]. Such a mechanism provides a conduit through which both the chemical and the social environment could affect our epigenome and thus gene expression and function (Fig.…”

Section: The Relationship Between Chromatin and Dna Methylationmentioning

confidence: 99%

“…Signaling pathways that result in increased cAMP also activate CBP [Chawla et al, 1998]. NGFI-A and CBP are recruited to the GR exon 1 7 promoter in response to maternal care which explains the increased acetylation and demethylation observed in offspring of high LG-ABN [Weaver et al, 2007]. Tissue culture experiments demonstrated that recruitment of NGFI-A to the GR exon 1 7 promoter resulted in replicationindependent DNA demethylation.…”

Section: Mechanism Linking Maternal Care and Epigenetic Reprogrammingmentioning

confidence: 99%

“…Tissue culture experiments demonstrated that recruitment of NGFI-A to the GR exon 1 7 promoter resulted in replicationindependent DNA demethylation. The recruitment of NGFI-A to the promoter facilitates the interaction of MBD2, a protein proposed to be involved in replication-independent DNA demethylation, with the promoter [Weaver et al, 2007]. Further experiments are required, including specific knock down of NGFI-A CBP and MBD2 in vivo to fully demonstrate the pathway linking exposure to maternal-care and demethylation of specific loci.…”

Section: Mechanism Linking Maternal Care and Epigenetic Reprogrammingmentioning

confidence: 99%

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The social environment and the epigenome

Szyf

McGowan

Meaney

2007

Environ and Mol Mutagen

451

222

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The genome is programmed by the epigenome. Two of the fundamental components of the epigenome are chromatin structure and covalent modification of the DNA molecule itself by methylation. DNA methylation patterns are sculpted during development and it has been a long held belief that they remain stable after birth in somatic tissues. Recent data suggest that DNA methylation is dynamic later in life in postmitotic cells such as neurons and thus potentially responsive to different environmental stimuli throughout life. We hypothesize a mechanism linking the social environment early in life and long-term epigenetic programming of behavior and responsiveness to stress and health status later in life. We will also discuss the prospect that the epigenetic equilibrium remains responsive throughout life and that therefore environmental triggers could play a role in generating interindividual differences in human behavior later in life. We speculate that exposures to different environmental toxins alters long-established epigenetic programs in the brain as well as other tissues leading to lateonset disease. Environ. Mol. Mutagen. 49:46-60, 2008. V V C 2007 Wiley-Liss, Inc.

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“…Alterations in NGFI-A expression have been observed in different brain regions and seem to be responsive to a variety of stimuli (e.g., Thompson and Rosen 2006). This factor has been associated to serotonin-induced DNA demethylation, and it is hypothesized that NGFI-A contributes to epigenetic programming of glucocorticoid receptor expression (Weaver et al 2007).…”

Section: Paroxetine-induced Effects On Glial Cells-implications For Nmentioning

confidence: 99%

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

et al. 2008

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Introduction Monoamine-based antidepressants inhibit neurotransmitter reuptake within short time. However, it commonly takes several weeks until clinical symptoms start to resolve-indicating the involvement of effects distant from reuptake inhibition. Objective To unravel other mechanisms involved in drug action, a "reverse" pharmacological approach was applied to determine antidepressant-induced alterations of hippocampal gene expression. Materials and methodsThe behavioral response to longterm paroxetine administration of male DBA/2Ola mice was assessed by the forced swim test (FST), the modified hole board (mHB), and the dark/light box. Hippocampi of test-naive mice were dissected, and changes in gene expression by paroxetine treatment were investigated by means of microarray technology. Results and discussion Robust effects of paroxetine on passive stress-coping behavior in the FST were observed. Furthermore, anxiolytic properties of long-term antidepressant treatment could be identified in DBA mice in both, the mHB and dark/light box. Analysis of microarray results revealed a list of 60 genes differentially regulated by chronic paroxetine treatment. Preproenkephalin 1 and inhibin beta-A showed the highest level of transcriptional change. Furthermore, a number of candidates involved in neuroplasticity/neurogenesis emerged (e.g., Bdnf, Gfap, Vim, Sox11, Egr1, Stat3). Seven selected candidates were confirmed by in situ hybridization. Additional immunofluorescence colocalization studies of GFAP and vimentin showed more positive cells to be detected in long-term paroxetine-treated DBA mice. Conclusion Candidate genes identified in the current study using a mouse strain validated for its responsiveness to long-term paroxetine treatment add, in our opinion, to unraveling the mechanism of action of paroxetine as a representative for SSRIs.

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The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes

Cited by 464 publications

References 40 publications

Environmental regulation of the neural epigenome

Environmental regulation of the neural epigenome

The social environment and the epigenome

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

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