Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Elizabeth A Heller, Hannah M Cates, Catherine J Peña, Haosheng Sun, Ningyi Shao, Jian Feng, Sam A Golden, James P Herman, Jessica J Walsh, Michelle Mazei-Robison, Deveroux Ferguson, Scott Knight, Mark A Gerber, Christian Nievera, Ming-Hu Han, Scott J Russo, Carol S Tamminga, Rachael L Neve, Li Shen, H Steve Zhang, Feng Zhang, Eric J Nestler

ABSTRACT

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior. More... »

PAGES

1720

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nn.3871

    DOI

    http://dx.doi.org/10.1038/nn.3871

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010852106

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25347353


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