References
Query Results -- Details
MGI Accession ID: MGI:3621508
J Number: J:107584
Other Accession IDs:
Title: Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum.
Authors: Kumar A; Choi KH; Renthal W; Tsankova NM; Theobald DE; Truong HT; Russo SJ; Laplant Q; Sasaki TS; Whistler KN; Neve RL; Self DW; Nestler EJ
Journal: Neuron
Volume: 48
Issue: 2
Date: 2005 Oct 20
Year: 2005
Pages: 303-14
Review Status: Peer Reviewed
Abstract:
Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. DeltaFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity.
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