Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

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 ZhangFeng Zhang, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone posttranslational 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.

Original languageEnglish (US)
Pages (from-to)1720-1727
Number of pages8
JournalNature neuroscience
Volume17
Issue number12
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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