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 journalArticle

112 Citations (Scopus)

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

Fingerprint

Epigenomics
Chromatin
Depression
Reward
Transcription Factors
Histone Code
Genes
Chromatin Assembly and Disassembly
Drug and Narcotic Control
Nucleus Accumbens
Brain
Street Drugs
Enzymes
Post Translational Protein Processing
Acetylation
Histones
Methylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Heller, E. A., Cates, H. M., Peña, C. J., Sun, H., Shao, N., Feng, J., ... Nestler, E. J. (2014). Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nature Neuroscience, 17(12), 1720-1727. https://doi.org/10.1038/nn.3871

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

In: Nature Neuroscience, Vol. 17, No. 12, 01.01.2014, p. 1720-1727.

Research output: Contribution to journalArticle

Heller, EA, Cates, HM, Peña, CJ, Sun, H, Shao, N, Feng, J, Golden, SA, Herman, JP, Walsh, JJ, Mazei-Robison, M, Ferguson, D, Knight, S, Gerber, MA, Nievera, C, Han, MH, Russo, SJ, Tamminga, CS, Neve, RL, Shen, L, Zhang, HS, Zhang, F & Nestler, EJ 2014, 'Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors', Nature Neuroscience, vol. 17, no. 12, pp. 1720-1727. https://doi.org/10.1038/nn.3871
Heller EA, Cates HM, Peña CJ, Sun H, Shao N, Feng J et al. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nature Neuroscience. 2014 Jan 1;17(12):1720-1727. https://doi.org/10.1038/nn.3871
Heller, Elizabeth A. ; Cates, Hannah M. ; Peña, Catherine J. ; Sun, Haosheng ; Shao, Ningyi ; Feng, Jian ; Golden, Sam A. ; Herman, James P. ; Walsh, Jessica J. ; Mazei-Robison, Michelle ; Ferguson, Deveroux ; Knight, Scott ; Gerber, Mark A. ; Nievera, Christian ; Han, Ming Hu ; Russo, Scott J. ; Tamminga, Carol S. ; Neve, Rachael L. ; Shen, Li ; Zhang, H. Steve ; Zhang, Feng ; Nestler, Eric J. / Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. In: Nature Neuroscience. 2014 ; Vol. 17, No. 12. pp. 1720-1727.
@article{af93297081224204be89b0909e0d6a01,
title = "Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors",
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.",
author = "Heller, {Elizabeth A.} and Cates, {Hannah M.} and Pe{\~n}a, {Catherine J.} and Haosheng Sun and Ningyi Shao and Jian Feng and Golden, {Sam A.} and Herman, {James P.} and Walsh, {Jessica J.} and Michelle Mazei-Robison and Deveroux Ferguson and Scott Knight and Gerber, {Mark A.} and Christian Nievera and Han, {Ming Hu} and Russo, {Scott J.} and Tamminga, {Carol S.} and Neve, {Rachael L.} and Li Shen and Zhang, {H. Steve} and Feng Zhang and Nestler, {Eric J.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/nn.3871",
language = "English (US)",
volume = "17",
pages = "1720--1727",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

AU - Heller, Elizabeth A.

AU - Cates, Hannah M.

AU - Peña, Catherine J.

AU - Sun, Haosheng

AU - Shao, Ningyi

AU - Feng, Jian

AU - Golden, Sam A.

AU - Herman, James P.

AU - Walsh, Jessica J.

AU - Mazei-Robison, Michelle

AU - Ferguson, Deveroux

AU - Knight, Scott

AU - Gerber, Mark A.

AU - Nievera, Christian

AU - Han, Ming Hu

AU - Russo, Scott J.

AU - Tamminga, Carol S.

AU - Neve, Rachael L.

AU - Shen, Li

AU - Zhang, H. Steve

AU - Zhang, Feng

AU - Nestler, Eric J.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925226532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925226532&partnerID=8YFLogxK

U2 - 10.1038/nn.3871

DO - 10.1038/nn.3871

M3 - Article

C2 - 25347353

AN - SCOPUS:84925226532

VL - 17

SP - 1720

EP - 1727

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 12

ER -