Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors.
Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors.
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DOI：
10.1038/nn.3871
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发表时间：
2014-12
影响因子：
25
通讯作者：
Nestler, Eric J.
中科院分区：
文献类型：
--
作者：
Heller, Elizabeth A.;Cates, Hannah M.;Pena, 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.
长期暴露于药物滥用或压力调节转录因子，染色质修饰酶，组蛋白翻译后修饰在离散的大脑区域。由于所涉及的酶的混杂性，目前还不可能获得直接的因果证据来暗示在单个基因处发生的染色质重塑对转录和随后的行为可塑性的调节。在这里，我们研究的机制，染色质动态神经生物学现象，通过应用工程转录因子选择性地修改染色质在体内特定的基因。我们发现，组蛋白甲基化或乙酰化的FosB基因座在核的大脑奖励区域，是足以控制药物和压力诱发的转录和行为反应，通过与内源性转录机制的相互作用。这种方法使我们能够将给定基因的表观遗传景观直接与其表达的调控及其对奖励行为的后续影响联系起来。
Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin modifying enzymes, and histone posttranslational modifications in discrete brain regions. Due to 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. Here, we investigate the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific gene in vivo. We found that histone methylation or acetylation at the FosB locus in nucleus accumbens—a brain reward region—is sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allows us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
12.3
作者：
Feng J;Wilkinson M;Liu X;Purushothaman I;Ferguson D;Vialou V;Maze I;Shao N;Kennedy P;Koo J;Dias C;Laitman B;Stockman V;LaPlant Q;Cahill ME;Nestler EJ;Shen L
通讯作者：
Shen L
影响因子：
64.8
作者：
Lachner, M;O'Carroll, N;Jenuwein, T
通讯作者：
Jenuwein, T
影响因子：
25
作者：
Kennedy, Pamela J.;Feng, Jian;Robison, A. J.;Maze, Ian;Badimon, Ana;Mouzon, Ezekiell;Chaudhury, Dipesh;Damez-Werno, Diane M.;Haggarty, Stephen J.;Han, Ming-Hu;Bassel-Duby, Rhonda;Olson, Eric N.;Nestler, Eric J.
通讯作者：
Nestler, Eric J.